Context-dependent cocaine sensitization: differential effect of haloperidol on development versus expression.
Repeated, intermittent administration of psychomotor stimulants has been shown to produce increasing effects (behavioral sensitization) in many species of animals. In a novel two-day sensitization paradigm, rats that received a single high dose of cocaine (40 mg/kg) compared with saline on day 1 showed an increased locomotor response to a challenge dose (10 mg/kg) on day 2. This effect is conditioned or context-dependent; i.e., it is only observed if the rats received cocaine in an environment similar to the test environment. If the cocaine-induced hyperactivity on day 1 is prevented with pharmacological agents such as haloperidol and diazepam, sensitization on day 2 does not occur. Furthermore, although moderate (0.2 mg/kg) and high doses (0.5 mg/kg) of haloperidol (day 1) prevented the development of sensitization to cocaine, they were ineffective when given prior to the day 2 challenge dose in preventing the expression of sensitization. Thus, this type of cocaine sensitization appears to involve conditioning, show stimulus generalization, and offer a possible model for clinical neuroleptic nonresponsiveness once stimulant-induced pathological behavior has been induced.
Weiss
S R
SR
Biological Psychiatry Branch, National Institute of Mental Health 20892.
Post
R M
RM
Pert
A
A
Woodward
R
R
Murman
D
D
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology*; D006702:Homing Behavior; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D003042:Cocaine; D006220:Haloperidol; D003975:Diazepam