Effects of the dopamine D-1 antagonist SCH 23390 microinjected into the accumbens, amygdala or striatum on cocaine self-administration in the rat.
This study tested the hypothesis that blockade of D-1 dopamine receptors in the nucleus accumbens shell, central nucleus of the amygdala or dorsal striatum by intracerebral microinjection of the dopamine antagonist SCH 23390 produces an attenuation of the effects of self-administered cocaine. Microinjection of SCH 23390 (0-4.0 micrograms total dose) into any of the three brain regions dose-dependently increased the rate of cocaine self-administration, consistent with a partial attenuation of the effects of cocaine under these conditions (0.25 mg cocaine i.v.; fixed-ratio 5 timeout 20 s). The regional rank order potency of SCH 23390 was accumbens > amygdala > striatum, striatal injections being equipotent with subcutaneous administration. Moreover, SCH 23390 produced rapid effects on cocaine self-administration only when injected into the accumbens or amygdala. The time course of this regional selectivity was consistent with the rate of diffusion of SCH 23390 from the site of injection as measured by quantitative autoradiography, demonstrating that the regional selectivity of intracerebral injections of SCH 23390 is time-dependent. These results support a role for D-1 dopamine receptors in the nucleus accumbens and amygdala in the effects of self-administered cocaine, and suggest that D-1 receptors in certain portions of the 'extended amygdala' may be an important substrate for the reinforcing actions of cocaine.
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
S B
SB
Caine
S C
SC
Heinrichs
V L
VL
Coffin
G F
GF
Koob
D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D002404:Catheterization; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008845:Microinjections; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology; D017072:Neostriatum / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D012646:Self Administration / Q000523:psychology
D001552:Benzazepines; D018492:Dopamine Antagonists; D009294:Narcotics; D017447:Receptors, Dopamine D1; D003042:Cocaine