Journal
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Volume 18, Issue 4, Pages 303-311Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.euroneuro.2007.08.003
Keywords
cocaine; self-administration; escalation; alpha-1 noradrenergic receptor; rats; bed nucleus of stria terminalis
Funding
- NATIONAL INSTITUTE ON DRUG ABUSE [K01DA022473, R01DA004398] Funding Source: NIH RePORTER
- NIDA NIH HHS [R01 DA004398-21, R01 DA004398, K01 DA022473] Funding Source: Medline
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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 (a, 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 tower in LgA rats than in ShA and drug-naive rats. In contrast, UK14304 (alpha(2) receptor agonist) and betaxotol (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. (c) 2007 Elsevier B.V. and ECNP. All rights reserved.
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