The Journal of Neuroscience, August 1, 2001, 21(15):5841-5846
Blockade of D1 Dopamine Receptors in the Ventral Tegmental Area
Decreases Cocaine Reward: Possible Role for Dendritically Released
Dopamine
Robert
Ranaldi1 and
Roy
A.
Wise2
1 Department of Psychology, Queens College, City
University of New York, Flushing, New York 11367, and
2 Behavioral Neuroscience Branch, Intramural Research
Program, National Institute on Drug Abuse, National Institutes of
Health, Baltimore, Maryland 21224
This study was designed to assess the involvement of D1 dopamine
actions in the ventral tegmental area (VTA) on intravenous cocaine
self-administration. Rats were trained to self-administer intravenous
injections of cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR-1) schedule or a progressive ratio (PR) schedule of reinforcement
and then were tested under the influence of bilateral VTA injections of
the D1 dopamine receptor antagonist SCH 23390 or the 5-HT2 receptor
antagonist ketanserin. SCH 23390 increased cocaine self-administration
on the FR-1 schedule but decreased it on the PR schedule. Injections of
ketanserin were ineffective, as were injections of SCH 23390 in a site
1 mm dorsal or 1 mm rostral to the effective VTA site. These data
suggest a role for dendritically released dopamine, presumably acting
through D1 receptors located on the axons of GABAergic or glutamatergic
inputs to the VTA, in the effectiveness of cocaine reward.
Key words:
drug abuse; reinforcement; dendritic release; motivation; operant learning; progressive ratio schedule
Copyright © 2001 Society for Neuroscience 0270-6474/01/21155841-06$05.00/0
