D1 dopamine receptors in the nucleus accumbens modulate cocaine self-administration in the rat.
Previous work using systemic injections of dopamine receptor antagonists has established that dopamine D1 receptors may have a role in cocaine self-administration. The purpose of the present study was to test the hypothesis that these effects were mediated by dopamine D1 receptors in the region of the nucleus accumbens. Animals were trained to perform operant responses to self-administer cocaine via an IV catheter on a fixed-ratio 5 (FR 5) schedule of reinforcement. SCH23390, a selective D1 dopamine antagonist, significantly increased the self-administration of cocaine when injected into the nucleus accumbens. This increase in self-administration is thought to reflect decreases in the magnitude of the reinforcer, similar to the increase observed when the dose of cocaine is reduced. Similar doses of SCH23390 injected into the posterior caudate nucleus failed to alter cocaine self-administration. These data suggest that D1 receptors in the nucleus accumbens are important for the reinforcing properties of cocaine.
Département de Chimie Organique, INSERM U. 266 Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
R
R
Maldonado
P
P
Robledo
A J
AJ
Chover
S B
SB
Caine
G F
GF
Koob
D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D003042:Cocaine