Involvement of the olfactory tubercle in cocaine reward: intracranial self-administration studies.
Cocaine has multiple actions and multiple sites of action in the brain. Evidence from pharmacological studies indicates that it is the ability of cocaine to block dopamine uptake and elevate extracellular dopamine concentrations, and thus increase dopaminergic receptor activation, that makes cocaine rewarding. Lesion studies have implicated the nucleus accumbens (the dorsal portion of the "ventral striatum") as the probable site of the rewarding action of the drug. However, the drug is only marginally self-administered into this site. We now report that cocaine (60 or 200 mm in 75 nl/infusion) is readily self-administered into the olfactory tubercle, the most ventral portion of the ventral striatum. Cocaine (200 mm) was self-administered marginally into the accumbens shell but not into the core, dorsal striatum, or ventral pallidum. In addition, cocaine injections (200 mm in 300 nl) into the tubercle but not the shell or ventral pallidum induced conditioned place preference. Rewarding effects of cocaine in the tubercle were blocked by coadministration of dopamine D1 or D2 antagonists (1 mm SCH 23390 or 3 mm raclopride) and were not mimicked by injections of the local anesthetic procaine (800 mm). In conclusion, the tubercle plays a critical role in mediating rewarding action of cocaine.
Ikemoto
Satoshi
S
Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA. sikemoto@intra.nida.nih.gov
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D004192:Discrimination, Psychological / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004333:Drug Administration Routes; D008297:Male; D009833:Olfactory Pathways / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration
D000779:Anesthetics, Local; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D003042:Cocaine