title: Alpha 1-noradrenergic system role in increased motivation for cocaine intake in rats with prolonged access.
abstract: In rodents, extended access to cocaine produces an escalation in cocaine self-administration that has face and construct validity for human compulsive drug intake. Here we report that rats with six-hour access (long access, LgA) to cocaine self-administration produced a higher breakpoint for cocaine using a progressive-ratio schedule than rats with one-hour access (short access, ShA), and prazosin (alpha 1 receptor antagonist) reduced the higher breakpoint for cocaine in LgA rats. Additionally, the number of neurons with alpha 1-adrenergic receptor-like immunoreactivity in the bed nucleus of stria terminalis (BNST) was found to be much lower in LgA rats than in ShA and drug-naive rats. In contrast, UK14304 (alpha 2 receptor agonist) and betaxolol (beta 1 receptor antagonist) had no effect on cocaine self-administration in either group. The data suggest that activation of the alpha 1-noradrenergic system, perhaps in the BNST, is associated with increased motivation for cocaine in rats with extended access.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, SP30-2400, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. sunmee@scripps.edu <sunmee@scripps.edu>
authors.forename: Sunmee
authors.initials: S
authors.lastname: Wee
authors.forename: Chitra D
authors.initials: CD
authors.lastname: Mandyam
authors.forename: Dusan M
authors.initials: DM
authors.lastname: Lekic
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015784:Betaxolol / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D000068438:Brimonidine Tartrate; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D009042:Motivation; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism / Q000502:physiology*; D012646:Self Administration; D012686:Septal Nuclei / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011810:Quinoxalines; D018340:Receptors, Adrenergic, alpha-1; D000068438:Brimonidine Tartrate; D015784:Betaxolol; D011224:Prazosin