title: Suppression of psychoactive effects of cocaine by active immunization.
abstract: Cocaine is a powerfully addictive substance and new strategies are needed to treat its abuse. Generating an active immunization to cocaine offers a means of blocking the actions of the drug by preventing it from entering the central nervous system, and should have fewer side effects than treatments based on manipulation of central neurotransmitter function. The design and preparation of a cocaine immunogen requires special regard for the stability of cocaine both free and as a haptenic determinant. Immunochemistry and a well defined behavioural model were brought together to address the problem of inactivation of the psychostimulant actions of cocaine. We report here that active immunization with a new, stable cocaine conjugate suppressed locomotor activity and stereotyped behaviour in rats induced by cocaine but not by amphetamine. Moreover, following acute injection of cocaine, levels of cocaine in the striatum and cerebellum of the immunized animals were lower than those of control animals. These results suggest that immunopharmacotherapy may be a promising means by which to explore new treatments for cocaine abuse.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Carrera
authors.forename: J A
authors.initials: JA
authors.lastname: Ashley
authors.forename: L H
authors.initials: LH
authors.lastname: Parsons
authors.forename: P
authors.initials: P
authors.lastname: Wirsching
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
authors.forename: K D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000493:pharmacokinetics; D006241:Haptens / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D018796:Immunoconjugates / Q000276:immunology; D008297:Male; D011597:Psychomotor Performance; D051381:Rats; D017208:Rats, Wistar; D019966:Substance-Related Disorders / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000906:Antibodies; D006241:Haptens; D018796:Immunoconjugates; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D003042:Cocaine