alpha(1)-Noradrenergic system role in increased motivation for cocaine intake in rats with prolonged access

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.