8-OH DPAT can restore the locomotor stimulant effects of cocaine blocked by haloperidol

In the first experiment, separate groups of rats (n = 7) were treated with either saline, cocaine (10 mg/kg), haloperidol (0.1 mg/kg), or cocaine (10 mg/kg) plus haloperidol (0.1 mg/kg). Locomotor behavior was measured in an open-field environment, and cocaine induced a reliable locomotor stimulant effect compared to saline-treated animals. Haloperidol produced a progressi ve decline in locomotion over the 5 test days. Haloperidol also blocked coc aine stimulant effects compared to cocaine-treated animals. In the second e xperiment, five groups (n = 7) of animals were treated either with saline, cocaine (10 mg/kg), 8-OH DPAT (0.2 mg/kg), 8-OH DPAT (0.2 mg/kg) plus halop eridol (0.1 mg/kg), or 8-OH DPAT (0.2 mg/kg) plus haloperidol 0.1 mg/kg plu s cocaine (10 mg/kg). Over the course of 5 days of treatment, cocaine induc ed a locomotor stimulant effect. Saline and 8-OH DPAT animals did not diffe r in terms of locomotion. The 0.1 mg/kg haloperidol plus 0.2 mg/kg 8-OH DPA T treatment decreased locomotion compared to the saline group, but the grou p given 0.2 mg/kg 8-OH DPAT plus 0.1 mg/kg haloperidol plus cocaine (10 mg/ kg) exhibited a locomotor stimulant effect equivalent to the cocaine group. In a third experiment, it was found that the 0.2 mg/kg 8-OH DPAT treatment did not enhance the locomotor stimulant effect of cocaine. Thus, the 8-OH DPAT treatment was able to restore a cocaine locomotor stimulant effect in animals treated with haloperidol without directly enhancing the lo comotor stimulant effects of cocaine. In Experiments 2 and 3, entries into the cent ral zone of the open field were measured. Cocaine reliably increased centra l zone entries. The 8-OH DPAT treatment, however, selectively blocked this behavioral effect of cocaine suggesting a qualitative influence of 5-HT1A r eceptors upon cocaine, independent of locomotion activation by cocaine. Ex vivo measurements of dopamine and 5-hydroxytryptamine metabolism in limbic tissue were consistent with the established effects of cocaine, haloperidol , and 8-OH DPAT upon dopamine and 5-hydroxytryptamine neurotransmission. In addition, measurement of cocaine brain concentration indicated that neithe r haloperidol or 8-OH DPAT affected cocaine concentration in brain. (C) 200 0 Elsevier Science Inc.