Effects of 5-HT1A receptor agonists and L-5-HTP in Montgomery's conflict test

Abstract The effects of the pyrimidinyl-piperazinesbuspirone, gepirone, ipsapirone and their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP) as well as of 8-hydroxy-2-(di- n -propylamino)tetralin (8-OH-DPAT) and L-5-hydroxytryptophan (L-5-HTP) were investigated in Montgomery's conflict test—an animal anxiety model based on the animal's inborn urge to explore a new environment and its simultaneous fear of elevated, open spaces. Subcutaneous buspirone (32–128 nmol/kg), gepirone (32–128 nmol/kg), ipsapirone (32–512 nmol/kg) and 8-OH-DPAT (50–200 nmol/kg), as well as intraperitoneal L-5-HTP (56 μmol/kg) produced anxiolytic-like effects. However, at higher doses the magnitude of these effects decreased and overall the dose-response curves displayed inverted U-shapes. The highest doses (2048 nmol/kg) of buspirone and of gepirone even decreased responding below control levels, possibly in part due to concomitant sedation/motor impairment. After L-5-HTP (448 μmol/kg) and PmP (512 nmol/kg) anxiogenic-like effects were observed. The results indicate that anxiolytic- and anxiogenic-like effects of drugs affecting central serotonergic neurotransmission can be obtained in a sensitive rat anxiety model which neither involves consummatory behavior nor punishment. The anxiolytic-like effects of these compounds may be due to their 5-HT 1A agonistic properties. Moreover, the present data may provide support for a possible reciprocal association of presynaptic 5-HT 1A receptors vs. postsynaptic 5-HT 1A as well as 5-HT 2 receptors with regard to anxiety.