BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF REPEATED ADMINISTRATION OF COCAINE IN RATS

The effects of repeated administration of cocaine (15 mg/kg, i.p. twice daily at 8-hr intervals) were investigated on the spontaneous motor activity (SMA) and stereotypy (ST) as well as on the various neurotransmitters (e.g. norepinephrine, NE; dopamine, DA; serotonin, 5-HT; acetylcholine, ACh) in different brain areas (e.g. diencephalon-midbrain, DM; pons-medulla, PM; caudate nucleus, CN) in rats. Following repeated injections of cocaine, both SMA and ST gradually increased, reaching a peak in each case on about the 9th day, then gradually decreased up to the 18th or 20th day, after which the activities were maintained at minimum level which was slightly higher than normal levels. Concomitantly, the DA level in the CN and DM increased and 5-HT in the DM and PM decreased reaching their maximum or minimum levels following cocaine injections on the 9th day; these changes were gradually minimized by the 18th day and remained so up to the 30th day. There were also slight changes in NE and ACh levels. It thus appears that, following repeated cocaine administrations, the changes in the drug-induced behavioural effects can be correlated roughly with the changes in the DA level in the CN and the 5-HT levels in the DM and PM. © 1978.