The role of D1 and D2 dopamine receptors in the acquisition and expression of cocaine-induced conditioned increases in locomotor behavior.
Certain motoric effects of cocaine increase in intensity with repetitive administration. Conditioned drug effects are among primary determinants of such sensitization. The purpose of these experiments was to evaluate the role of D1 and D2 dopamine (DA) receptor mechanisms in the acquisition and expression of cocaine conditioning. On Day 1, rats were injected with cocaine (40mg/kg) either before (PAIRED) or after (UNPAIRED) exposure to a locomotor activity chamber. On Day 2, all animals were injected with a low dose of cocaine (10mg/kg) prior to placement in the locomotor chambers. Conditioning on Day 2 was evidenced by significantly higher activity levels in the PAIRED group relative to the UNPAIRED or saline-treated groups. Pretreatment with D1 (SCH 23390) or D2 (raclopride, sulpiride, haloperidol) DA antagonists on Day 1 prevented the development of conditioning as assessed on Day 2, indicating that both receptor subtypes are involved in acquisition. However, pretreatment with raclopride or SCH 23390 on Day 2, prior to cocaine injections, did not eliminate the differences in behavior between the conditioned and non-conditioned groups. Neither D1 (SKF 82958, SKF 38393) nor D2 (quinpirole) agonists administered alone were effective in establishing conditioning, while a combination of SKF 82958 and quinpirole was effective, suggesting that conditioning in this experimental paradigm requires the concurrent activation of both receptor subtypes. In the final study it was found that conditioned cocaine effects could be revealed only in the presence of quinpirole or apomorphine on Day 2. The D1 agonists (SKF 38393 and SKF 82958) were ineffective. This would suggest either that only quinpirole and apomorphine are effective in amplifying the conditioned effects of cocaine on Day 2 or that the cues produced by these drugs are more similar to those produced by cocaine than those produced by D1 agonists.
Fontana
D.
D
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892, USA.
Post
R.M.
RM
Weiss
S.R.B.
SR
Pert
A.
A