Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in a D1 dopamine receptor dependent manner.
The effect of previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) on the subsequent self-administration of cocaine was assessed. Rats in different groups were pre-exposed to three injections into the VTA of either saline (0.5 microl/side) or AMPH (2.5 microg/0.5 microl/side). Injections were given once every third day. Starting 7-10 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.3 mg/kg/infusion) under fixed ratio 1 and 2 (FR1 and FR2) schedules and then tested under a progressive ratio (PR) schedule of reinforcement for six consecutive days. No differences between groups were observed during self-administration training under the FR schedules of reinforcement. However, when tested under the PR schedule, VTA AMPH pre-exposed rats worked more and, as a result, obtained more infusions of cocaine than saline pre-exposed rats. Rats in a separate group pre-exposed to VTA AMPH but co-infused with the D(1)-like dopamine (DA) receptor antagonist SCH23390 (0.25 microg/0.5 microl/side) did not show enhanced cocaine self-administration. These rats, as well as others pre-exposed to VTA SCH23390 alone showed levels of cocaine self-administration similar to saline pre-exposed rats. Thus, in a manner paralleling the sensitization of AMPH-induced locomotion and nucleus accumbens DA overflow, previous exposure to AMPH in the VTA leads to enhanced intravenous self-administration of cocaine and activation of D(1) DA receptors in this site during pre-exposure is necessary for the production of this effect.
Suto
N
N
Department of Psychology, The University of Chicago, Chicago, IL 60637, USA.
Austin
J D
JD
Tanabe
L M
LM
Kramer
M K
MK
Wright
D A
DA
Vezina
P
P
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D012055:Reinforcement Schedule; D012646:Self Administration / Q000523:psychology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D017447:Receptors, Dopamine D1; D000661:Amphetamine; D003042:Cocaine