The effects of the 5-hydroxytryptamine(1A) agonist 8-hydroxy-2-(di-n-propylamino) tetralin on spontaneous activity, cocaine-induced hyperactivity andbehavioral sensitization: A microanalysis of locomotor activity

The influence of the 5-hydroxytryptamine(1A) agonist 8-hydroxy-2-(di-n-prop ylamino)tetralin (DPAT) on locomotor hyperactivity induced by the acute and chronic administration of cocaine was assessed. Horizontal activity was me asured in the periphery and center of an open field test enclosure equipped with photobeams; vertical activity was also recorded. Peripheral hyperacti vity induced by an acute administration of cocaine (10 or 20 mg/kg) was sig nificantly enhanced by 0.2 mg/kg DPAT. In contrast, central and vertical ac tivities were reduced in a dose-related manner by DPAT (0.1 and 0.2 mg/kg); DPAT also suppressed central (0.2 mg/kg) and vertical (0.1 and 0.2 mg/ kg) activities when administered alone. Similar observations were made on day 1 of chronic treatment with DPAT (0, 0.1, or 0.2 mg/kg) injected 15 min bef ore an injection of cocaine (0, 10, or 15 mg/kg) administered twice daily f or 7 days. By day 7 of repeated DPAT treatment, sensitization of DPAT-evoke d peripheral activity developed, which contrasted with tolerance to the cen tral and vertical hypoactivity evoked by DPAT. Sensitization developed to t he repeated treatment with 15 mg/ kg cocaine but not 10 mg/kg cocaine. Inte restingly, enhancements of all activity measures were observed between days 1 and 7 in rats cotreated with DPAT plus either dose of cocaine. This sens itization to DPAT plus cocaine was expressed on challenge with DPAT and coc aine but not with cocaine alone. The present study implies that the stimula tion of 5-hydroxytryptamine(1A) receptors is capable of modulating the hype ractivity evoked by cocaine, possibly via modulation of the mesoaccumbens d opamine circuit thought to mediate the behavioral effects of cocaine.