The dopamine D-1 receptor antagonist SCH 23390 injected into the dorsolateral bed nucleus of the stria terminalis decreased cocaine reinforcement in the rat.
The effects of bilateral intracranial injections of the D-1 dopamine receptor antagonist SCH 23390 HCl (0, 0.8, 1.6, 3.2, and 6.4 microgram total bilateral dose) administered into the dorsolateral bed nucleus of the stria terminalis (dlBNST) immediately prior to a 3 h intravenous cocaine self-administration session were examined. In addition, anatomical control injections of the most effective dose of SCH 23390 HCl (6.4 micogram) were made either 1.5 mm dorsal to the dlBNST or into the lateral ventricle. Injections directly into the dlBNST, but not those dorsal to the dlBNST or into the lateral ventricle, significantly increased the rate of cocaine self-administration within the first 20 min of the self-administration session, consistent with a partial attenuation of the reinforcing effects of cocaine under a fixed-ratio schedule of reinforcement (0.25 mg cocaine iv; fixed-ratio 5, timeout 20 s). Injections into all three sites increased cocaine self-administration across the entire 3 h session. These results suggest a role for D-1 dopamine receptors in the dlBNST in the reinforcing properties of self-administered cocaine, and also support the hypothesis that D-1 dopamine receptors in the 'extended amygdala' may play a significant role in cocaine self-administration.
Epping-Jordan
M P
MP
Department of Neuropharmacology, Division of Psychopharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Markou
A
A
Koob
G F
GF
D000679:Amygdala / Q000502:physiology; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012054:Reinforcement, Psychology; D012646:Self Administration; D013787:Thalamic Nuclei / Q000187:drug effects / Q000502:physiology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D009294:Narcotics; D017447:Receptors, Dopamine D1; D003042:Cocaine