Blockade of substantia nigra dopamine D1 receptors reduces intravenous cocaine reward in rats.
BACKGROUND
We have recently found that blockade of dopamine D1-type receptors in the ventral tegmental area reduces the rewarding effects of intravenous cocaine; here, we explored the possibility that blockade of D1 receptors in the adjacent substantia nigra (SN)--not usually considered part of reward circuitry--might have similar effects.


OBJECTIVE
To test the hypothesis that blockade of dopamine D1 receptors in the SN reduces the rewarding effects of cocaine.


METHODS
Twenty one rats were prepared with intravenous catheters and with bilateral guide cannulae implanted such that injections could be made directly into the SN or just dorsal to the SN. The rats were trained to self-administer intravenous cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR1) schedule of reinforcement. After stable responding developed, 13 of the animals were tested following pretreatment with bilateral microinjections of SCH 23390 at doses of 0, 1, 2 or 4 microg/0.5 microl into the SN and 8 were tested with injections of 0 microg or 4 microg/0.5 microl into a site 2 mm dorsal to the SN site.


RESULTS
Microinjections of SCH 23390 in the SN significantly increased rates of cocaine self-administration, while injections dorsal to SN had no significant effect on responding.


CONCLUSIONS
These data suggest that blockade of dendritically released DA in the SN reduces the rewarding effects of cocaine. These findings complement accumulating evidence that the rewarding effects of cocaine are not restricted to the drug's ability to elevate dopamine levels in the nucleus accumbens.
Quinlan
Matthew G
MG
Department of Psychology, Queens College, CUNY, 65-30 Kissena Boulevard, Flushing, NY 11367, USA.
Sharf
Ruth
R
Lee
David Y
DY
Wise
Roy A
RA
Ranaldi
Robert
R
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology; D003712:Dendrites / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008845:Microinjections; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration / Q000523:psychology; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D001552:Benzazepines; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D003042:Cocaine; D004298:Dopamine