Psychostimulant-induced activity is attenuated by two putative dopamine release inhibitors

Centrally administered amphetamine (AMPH), cathinone, (CATH), or cocaine (COC) have each been shown to produce elevated activity in rats and this effect is dose responsive. The question remains whether these psychostimulants share a common mechanism of action (i.e., do these psychostimulants act by releasing dopamine to increase activity levels?). Experiments were, therefore, conducted to measure the spontaneous activity of these three centrally administered psychostimulants in rats following pretreatment with two putative dopamine release inhibitors, viz., 5-(4-methyl-1 piperazinyl)imidazol(2,1-b) (1,3,5)-benzothiadiazepine maleate [CGS 10746B (CGS); 20 mg/kg)] and 4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicar boxylic acid methyl 1-methyl-ethyl ester [isradipine (ISR); 2.5 mg/kg)]. Rats fitted with chronic indwelling ventricular cannulae received a single dose of ICV-administered CATH (32 micrograms), AMPH (16 micrograms), COC (100 micrograms), or vehicle. Selection of these ICV doses of stimulant drugs was based upon results obtained in preliminary studies that indicated similar elevations of activity. ICV administration of each of these drugs/doses was preceded (20 min) by peripherally administered CGS, ISR, or vehicle. Results show that ICV CATH (32 micrograms), AMPH (16 micrograms), COC (100 micrograms) equieffectively elevate activity (two- to threefold) and that, in each case, this increase was significantly attenuated by pretreatment with CGS or ISR.