Differential blockade of chronic versus acute effects of intravenous cocaine by dopamine receptor antagonists. 1994

S R Tella
Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007.

The objectives of this study were to investigate behavioral sensitization to repeated once daily IV injections of cocaine, and to determine whether dopamine receptor antagonists differentially block chronic versus acute cocaine effects. Acute cocaine (0.3-3.0 mg/kg) produced a dose-dependent increase in both horizontal and stereotypic movements in male Sprague-Dawley rats. Repeated once daily injections of 1 or 3 mg/kg of cocaine augmented these effects. Pretreatment with either the D2 dopamine receptor antagonist haloperidol (0.03-0.3 mg/kg) or the D1 dopamine receptor antagonist R(+)-SCH-23390 (0.003-0.1 mg/kg) dose dependently attenuated cocaine's behavioral effects in both sensitized and cocaine-naive animals. There was a rightward shift in the dose-effect relationship of these antagonists in blocking the expression of behavioral sensitization as compared to their ability to block the acute behavioral effects of cocaine. These results indicate that repeated once daily IV injections of cocaine produced behavioral sensitization and both D1 and D2 dopamine receptor antagonists attenuated the expression of this sensitization. The data also suggest that dopamine receptor antagonists were more potent in blocking cocaine's effects in cocaine-naive animals than in cocaine-sensitized animals.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008297 Male Males
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006220 Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) Haldol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D001552 Benzazepines Compounds with BENZENE fused to AZEPINES.
D013239 Stereotyped Behavior Relatively invariant mode of behavior elicited or determined by a particular situation; may be verbal, postural, or expressive. Behavior, Stereotyped,Behaviors, Stereotyped,Stereotyped Behaviors
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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