5-HT1A AGONISTS INDUCE HIPPOCAMPAL THETA-ACTIVITY IN FREELY MOVING CATS - ROLE OF PRESYNAPTIC 5-NT1A RECEPTORS

Electrical activity in the dorsal hippocampus was recorded in freely m oving cats in response to intravenous administration of 5-HT1A agonist and antagonist drugs. Administration of low doses of the selective 5- HT1A agonists 8-OH-DPAT (5-20 mu g/kg) and ipsapirone (20-100 mu g/kg) produced rhythmic slow activity (theta) in rbe hippocampal EEC within 30 s. Similar effects were observed with BMY 7378 (20 and 100 mu g/kg ), which acts as an agonist at presynaptic (somatodendritic) 5-HT1A re ceptors and as an antagonist at postsynaptic 5-HT1A receptors. Power s pectral analysts showed that ail three compounds produced a dose-depen dent increase in the EEG power occurring in the theta frequency band ( 3.5-8.0 Hz) as a proportion of total power from 0.25 to 30.0 Hz (relat ive theta power). The increase in relative theta power produced by 8-O H-DPAT (20 mu g/kg) was greatly attenuated by spiperone (1 mg/kg), a h ighly effective 5-HT1A autoreceptor antagonist. Administration or spip erone alone had no significant effect on relative theta power. These r esults are discussed in relationship to the effects of these drugs on serotonergic neuronal activity. Our results suggest that preferential activation of presynaptic 5-HT1A receptors, and subsequent inhibition of serotonin neurotransmission, facilitates the appearance of hippocam pal theta activity in awake cats.