The role of the dorsal striatum during drug-seeking after abstinence from chronic cocaine self-administration

ALEJANDRA M PACCHIONI,; AMANDA GABRIELE,; RONALD E SEE.

Bethesda, MD,USA

Congreso; 8th Annual International conference of National Hispanic Science Network on Drug of Abuse; 2008

National Hispanic Science Network on Drug of Abuse

<!-- /* Font Definitions */ @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-1610611985 1107304683 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0in; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman";} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:10.0pt; mso-ansi-font-size:10.0pt; mso-bidi-font-size:10.0pt; mso-ascii-font-family:Calibri; mso-fareast-font-family:Calibri; mso-hansi-font-family:Calibri;} @page Section1 {size:8.5in 11.0in; margin:1.0in 1.0in 1.0in 1.0in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1;} --> Understanding the neural mechanisms that underlie relapse to drug abuse will ultimately lead us to develop new medications for addiction treatment. Animal models of the reinstatement of drug-seeking have been extensively used to model relapse in humans. In these paradigms, animals are first trained to operantly respond for i.v. drug infusions.  Drug self-administration is usually followed by extinction trials to bring responding down to low levels prior to triggering reinstatement with conditioned cues, drugs, or stress.  However, relapse in humans generally occurs after periods of abstinence in the absence of explicit extinction trials.  Moreover, we and others have previously shown that cocaine-seeking after either extinction or abstinence depends upon intact function of different brain regions.  For instance, the dorsolateral striatum (an area associated with habit learning) is required under both conditions, while the medial prefrontal cortex (an area associated with decision making) is only necessary after explicit extinction. The current study further evaluated the contribution of the dorsolateral striatum (dlCPu) to cocaine-seeking following extensive cocaine use and long periods of abstinence. We predicted that the dlCPu contribution would become more important after more prolonged cocaine consumption and longer periods of abstinence.  We examined relapse of cocaine-seeking in the previous cocaine-taking context (self-administration chamber) after 1, 14, and 60 days of abstinence in groups with different cocaine-taking histories.  Following implantation of a jugular catheter and bilateral intracranial guide cannulae, all animals were trained to press a lever along a FR-1 schedule of reinforcement for cocaine infusions (0.2 mg cocaine/50 ul/infusion).  Cocaine self-administration consisted of 5-6 days of 2-hr sessions with at least 10 cocaine infusions per session.  Subjects were then divided into two groups: short access (5 days of 2-hr sessions) or long access (15 days of 6-hr sessions).  After the last cocaine self administration session, animals underwent three separate relapse tests at days 1, 14, and 60, during which lever responding was recorded, but had no programmed consequences.  In between testing, animals remained in their home cages. For each relapse test, subjects received bilateral infusion of vehicle or a combination of a GABA-B and GABA-A agonist mixture (baclofen/muscimol, 1.0/0.1 mM) into the dlCPu prior to being placed in the self-administration chamber for a 2-hr test session.  Preliminary observations suggest that the contribution of the dlCPu during context induced relapse becomes more important after longer periods of drug intake and longer periods of abstinence