Effects of 5HT-1A agonists on locomotor and investigatory behaviors in rats differ from those of hallucinogens

Behavioral profiles composed of both locomotor activity and investigatory behavior were established for the 5HT-1A agonists 8OHDPAT, buspirone, gepirone, and ipsapirone using rats tested in a Behavioral Pattern Monitor. Typically these compounds dose-relatedly decreased horizontal locomotion and investigatory activity during the first half of the 1-h test session. Time-course studies revealed that the time interval between injection and placement of the animal in the testing chamber made no difference in the temporal distribution of locomotor activity following most 5HT-1A agonists. These results were compared and contrasted to the behavioral profiles previously established for hallucinogenic compounds such as LSD and DOM, the psychoactive properties of which have been suggested to be mediated by 5HT-2 binding sites. Examination of ipsapirone and 8OHDPAT in a familiar environment paradigm revealed that both drugs decreased behavioral responding independently of the animals' familiarity with the test environment, in contrast to the behaviorally suppressive effects of hallucinogenic 5HT-2 antagonists which disappear in a familiar environment. Additionally, d,l-propranolol was used as a 5HT-1 antagonist and was found to block the behavioral effects of the 5HT-1A agonists ipsapirone and buspirone without having significant effects by itself. Propranolol was also used to identify the contribution of the 5HT-1 binding site to the behavioral effects of LSD. Even at relatively high doses, propranolol only partially antagonized the effects of LSD, supporting the hypothesis that the behavioral effects of LSD reflect the activation of both 5HT-1 and 5HT-2 receptors. Together, these findings demonstrate that 5HT-1A agonists have a different profile of behavioral effects than 5HT-2 agonists and that the two classes of drugs can be differentiated using the same test paradigm. The results provide further support for the hypothesis that the previously described potentiation of neophobia induced by hallucinogens is due to the activation of 5HT-2 receptors.