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<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="QO5RTVuEQbHyvHObc07yxrAvDkW6XSZn7BPWwLX0qMu2p8U1PjKA1z69boEiQtxH">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="QO5RTVuEQbHyvHObc07yxrAvDkW6XSZn7BPWwLX0qMu2p8U1PjKA1z69boEiQtxH">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="QO5RTVuEQbHyvHObc07yxrAvDkW6XSZn7BPWwLX0qMu2p8U1PjKA1z69boEiQtxH">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="QO5RTVuEQbHyvHObc07yxrAvDkW6XSZn7BPWwLX0qMu2p8U1PjKA1z69boEiQtxH">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="QO5RTVuEQbHyvHObc07yxrAvDkW6XSZn7BPWwLX0qMu2p8U1PjKA1z69boEiQtxH">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="21766168">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://doi.org/10.1007/s00213-011-2409-y"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3055&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21766168&amp;db=pubmed&amp;nlmid=7608025"
title="See full text options at Springer"
data-ga-category="full_text"
data-ga-action="Springer"
data-ga-label="21766168"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif" alt="Springer full text link"><span class="text">
Springer
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/21766168/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21766168&amp;db=pubmed&amp;nlmid=7608025"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="21766168"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/21766168/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/21766168/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="21766168" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F21766168%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="QO5RTVuEQbHyvHObc07yxrAvDkW6XSZn7BPWwLX0qMu2p8U1PjKA1z69boEiQtxH"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
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Abstract
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<p>
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Rationale and objectives:
</strong>
Our knowledge about genes involved in the control of basal motor activity that may contribute to the pathology of the hyperactivity disorders, e.g., attention deficit hyperactivity disorder (ADHD), is limited. Disruption of monoamine neurotransmitter signaling through G protein-coupled receptors (GPCR) is considered to be a major contributing factor to the etiology of the ADHD. Genetic association evidence and functional data suggest that regulators of G protein signaling proteins of the R7 family (R7 RGS) that form obligatory complexes with type 5 G protein beta subunit (Gβ5) and negatively regulate signaling downstream from monoamine GPCRs may play a role in controlling hyperactivity.
</p>
<p>
<strong class="sub-title">
Methods:
</strong>
To test this hypothesis, we conducted behavioral, pharmacological, and neurochemical studies using a genetic mouse model that lacked Gβ5, a subunit essential for the expression of the entire R7 RGS family.
</p>
<p>
<strong class="sub-title">
Results:
</strong>
Elimination of Gβ5-RGS complexes led to a striking level of hyperactivity that far exceeds activity levels previously observed in animal models. This hyperactivity was accompanied by motor learning deficits and paradoxical behavioral sensitization to a novel environment. Neurochemical studies indicated that Gβ5-RGS-deficient mice had higher sensitivity of inhibitory GPCR signaling and deficits in basal levels, release, and reuptake of dopamine. Surprisingly, pharmacological treatment with monoamine reuptake inhibitors failed to alter hyperactivity. In contrast, blockade of NMDA receptors reversed the expression of hyperactivity in Gβ5-RGS-deficient mice.
</p>
<p>
<strong class="sub-title">
Conclusions:
</strong>
These findings establish that Gβ5-RGS complexes are critical regulators of monoamine-NMDA receptor signaling cross-talk and link these complexes to disorders that manifest as hyperactivity, impaired learning, and motor dysfunctions.
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<p> Figure 1. Gβ5 <sup> / </sup> mice display dramatic… </p>
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<p> Figure 1. Gβ5 <sup> / </sup> mice display dramatic hyperactivity, impaired habituation to novel environment and marked… </p>
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Figure 1. Gβ5<sup>/</sup> mice display dramatic hyperactivity, impaired habituation to novel environment and marked motor learning deficits
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<div class="figure-caption-contents">Behavior of Gβ5<sup>/</sup>mice and their wild-type littermates (Gβ5<sup>+/+</sup>) in the open field chamber (A-F). <b><i>A</i></b>, Gβ5<sup>/</sup>mice display paradoxical habituation to the novel environment and severe hyperactivity. ANOVA analysis revealed a significant habituation effect for both wild type (F<sub>(10,35)</sub> = 129.9, p &lt; 0.001) and Gβ5<sup>/</sup> (F<sub>(10,35)</sub> = 83.8, p &lt; 0.001). However, the direction of the effect was opposite: Gβ5<sup>+/+</sup> mice showed progressive decrease in activity during habituation, whereas the activity of Gβ5<sup>/</sup> mice increased. This difference in the habituation behavior was found significant by two-way ANOVA analysis (genotype x trial interaction, F<sub>(35, 720)</sub> = 3.14, p &lt; 0.001). Right panel shows habituation behavior of wild-type subjects on magnified scale. <b><i>B-F</i></b>, Quantification of typical mouse behavioral traits in the open field. Statistical significance of differences was analyzed using pair-wise comparison by Students t-test; **p &lt; 0.01 (n=11/group). <b><i>G</i></b>, Gβ5<sup>/</sup>mice exhibit severe deficits in motor learning behavior in rotarod test. A two-way ANOVA analysis revealed significant effect of trial for both groups of mice (F<sub>(10,187)</sub> = 7.38, p &lt; 0.001), genotype (F<sub>(1,187)</sub> = 120.25, p &lt; 0.001) and interaction between trial and genotype (F<sub>(10,187)</sub> = 2.248, p &lt; 0.05). Pairwise comparions by <i>post hoc</i> Tukeys test revealed that Gβ5<sup>/</sup>mice had a deficit in rotarod performance from the third trial (**, p &lt; 0.01).</div>
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<p> Figure 2. Subcellular localization of Gβ5 in… </p>
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<p> Figure 2. Subcellular localization of Gβ5 in the striatum and hippocampus </p>
</strong>
<div class="figure-caption-contents"><p> Electron micrographs show immunolabeling… </p></div>
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Figure 2. Subcellular localization of Gβ5 in the striatum and hippocampus
</strong>
<div class="figure-caption-contents">Electron micrographs show immunolabeling for Gβ5 in different neuronal compartments of WT mice, as detected using a pre-embedding immunogold method. In striatum <b><i>(A-C)</i></b>, and hippocampus (<b>D-F</b>) immunoparticles for Gβ5 were detected postsynaptically along the somatic plasma membrane (arrows), and intracellular sites (crossed arrows) of dendritic shafts (Den) and dendritic spines (s. In addition, immunoparticles for Gβ5 were detected at presynaptic sites, along the extrasynaptic plasma membrane (arrowheads) of axon terminals (at) establishing excitatory synapses with dendritic shafts or dendritic spines (s). Immunoreactivity for Gβ5 was completely absent in Gβ5<sup>/</sup>samples (<b>C,F</b>). Scale bar: 0.2 μm.</div>
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<p> Figure 3. Dynamics of striatal dopamine transmission… </p>
</strong>
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<strong class="figure-label">
<p> Figure 3. Dynamics of striatal dopamine transmission in Gβ5 <sup> / </sup> mice </p>
</strong>
<div class="figure-caption-contents"><b> <i> A </i> </b> , Measurements of basal extracellular…</div>
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<strong class="figure-label">
Figure 3. Dynamics of striatal dopamine transmission in Gβ5<sup>/</sup>mice
</strong>
<div class="figure-caption-contents"><b><i>A</i></b>, Measurements of basal extracellular levels of dopamine in the striatum of freely moving mice by microdialysis. <b><i>B</i></b>, Measurements of fast changes in dopamine release and re-uptake in coronal slices containing the striatum by cyclic voltammetry. Dopamine release was evoked by a single electrical pulse as indicated by arrow. Extracellular DA was sampled every 100 ms. Asterisk denotes statistically significant difference (*p &lt; 0.05) as revealed by Students t-test. <b><i>C and D</i></b>, Quantification of kinetic parameters of dopamine concentration changes suggesting slower dopamine release and clearance in response to electrical stimulation in Gβ5<sup>/</sup>striatal slices. Clearance parameters were obtained by fitting recordings to a single exponential decay and analyzed by Students t-test (*p &lt; 0.05, **p &lt; 0.01 for pair-wise comparisons between wild-type (Gβ5<sup>+/+</sup>) and Gβ5<sup>/</sup>mice.</div>
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<p> Figure 4. Enhanced GPCR signaling in Gβ5… </p>
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<strong class="figure-label">
<p> Figure 4. Enhanced GPCR signaling in Gβ5 <sup> / </sup> mice </p>
</strong>
<div class="figure-caption-contents"><b> <i> A </i> </b> , Gβ5 <sup> / </sup> mice exhibit greater morphine-induced…</div>
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<strong class="figure-label">
Figure 4. Enhanced GPCR signaling in Gβ5<sup>/</sup>mice
</strong>
<div class="figure-caption-contents"><b><i>A</i></b>, Gβ5<sup>/</sup>mice exhibit greater morphine-induced analgesia but normal nociceptive thresholds in the hot plate test (n=7 9) when compared with their wild-type littermates. A two-way ANOVA (doses by genotype) revealed a significant effect of dose (F<sub>(4,58)</sub> = 92.278, p &lt; 0.001) indicating analgesic effect of morphine in both genotypes and significant difference between genotypes (F<sub>(1,58)</sub> = 61.339, p &lt; 0.001). Gβ5<sup>/</sup>had higher sensitivity to morphine effects as indicated by the interaction between dose and genotype (F<sub>(4,58)</sub> = 13.804, p &lt; 0.001). Pairwise <i>post hoc</i> Tukeys test confirmed a significance of morphine effects (*p &lt; 0.05; **p &lt; 0.01, ***p &lt; 0.001 morphine vs saline control) and differences between genotypes (###, p &lt; 0.001). <b>B,</b> Elevated behavioral sensitivity of Gβ5<sup>/</sup>mice to motor depressant effects of the D2 receptor agonist quinpirole. Locomotor activity of wild-type Gβ5<sup>+/+</sup> (n=6) and Gβ5<sup>/</sup>(n= 6) mice was measured in the open field chamber for 3 hr following i.p. drug administration and then normalized to the activity of saline-treated controls of the same genotype. ANOVA showed quinpirole had significant inhibitory effect on activity of both Gβ5<sup>+/+</sup> (F<sub>(4,25)</sub>=13.137, p &lt; 0.001) and Gβ5<sup>/</sup>mice (F<sub>(4,25)</sub>=20.462, p &lt; 0.001). <i>Post hoc</i> Tukeys test confirmed higher doses of quinpirole inhibited mice activity (*p &lt; 0.05; **p &lt; 0.01, ***p &lt; 0.001 vs saline control). ANOVA analysis followed by Tukuey test showed significant difference at dose of 0.1 mg/kg between genotypes ( <sup>#</sup>p &lt; 0.05, Gβ5<sup>/</sup>mice vs Gβ5<sup>+/+</sup>). <b>C</b>, Elevated behavioral sensitivity of Gβ5<sup>/</sup>mice to motor depressant effects of the mGluR2/3 receptor agonist LY379268. Locomotor activity of wild-type Gβ5<sup>+/+</sup> (n=6) and Gβ5<sup>/</sup>(n= 6) mice was measured in the open field chamber for 3 hr following i.p. drug administration and then normalized to the activity of saline-treated controls of the same genotype. ANOVA showed LY379268 had significant inhibitory effect on activity of Gβ5<sup>/</sup>mice (F<sub>(4,25)</sub>=33.596, p &lt; 0.001). Pairwise <i>post hoc</i> Tukeys test confirmed higher doses of LY379268 inhibited activity of Gβ5<sup>/</sup>mice (***p &lt; 0.001 vs saline control). ANOVA analysis followed by Tukeys test showed significant difference at dose of 1.5 mg/kg between genotypes ( <sup>#</sup>p &lt; 0.05, Gβ5<sup>/</sup>mice vs wild-type). Error bars represent SEM values.</div>
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<p> Figure 5. Gβ5 <sup> / </sup> mice are resistant… </p>
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<strong class="figure-label">
<p> Figure 5. Gβ5 <sup> / </sup> mice are resistant to the effects of monoamine reuptake inhibitors </p>
</strong>
<div class="figure-caption-contents"><p> Mice (n=6/group)… </p></div>
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<strong class="figure-label">
Figure 5. Gβ5<sup>/</sup> mice are resistant to the effects of monoamine reuptake inhibitors
</strong>
<div class="figure-caption-contents">Mice (n=6/group) were injected i.p. with desipramine (10 mg/kg), atomoxine (10 mg/kg), citalopram (10 mg/kg) or amphetamine (1 mg/kg). Immediately after injection, mice were placed in an open field chamber and their activity was monitored for 2 hrs. Total distances run by animals after drug injection were normalized to those after the injection of saline. Statistically significant differences have been analyzed by Students t-test comparing drug-treated subjects and saline injected controls. (*p < 0.05, **p < 0.01 vs saline control). All error bars represent SEMs.</div>
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<p> Figure 6. Paradoxical effects of NMDA receptor… </p>
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<p> Figure 6. Paradoxical effects of NMDA receptor blockade in mice lacking Gβ5 </p>
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<div class="figure-caption-contents"><p> Gβ5 <sup> / </sup> mice… </p></div>
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Figure 6. Paradoxical effects of NMDA receptor blockade in mice lacking Gβ5
</strong>
<div class="figure-caption-contents">Gβ5<sup>/</sup>mice or their wild-type littermates (n=5) were injected either with saline or various doses of MK-801 and their ambulatory activities were monitored in the open field chamber. The same subjects were used to test the different MK-801doses with 2 days allowed between treatments. ANOVA revealed a significant effect of MK-801 on activity of both Gβ5<sup>+/+</sup> (F<sub>(4,29)</sub> = 6.896, p &lt; 0.001) and Gβ5<sup>/</sup> (F<sub>(4,29)</sub> = 34.921, p &lt; 0.001) mice. Pairwise <i>post hoc</i> Tukeys test revealed significant differences between treatments and saline control when indicated (*p &lt; 0.05; **p &lt; 0.01). Error bars represent SEMs.</div>
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