5-HT1A agonists induce hippocampal theta activity in freely moving cats: role of presynaptic 5-HT1A receptors

Electrical activity in the dorsal hippocampus was recorded in freely moving cats in response to intravenous administration of 5-HT_1A agonist and antagonist drugs. Administration of low doses of the selective 5-HT_1A agonists 8-OH-DPAT (5–20 μg/kg) and ipsapirone (20–100 μg/kg) produced rhythmic slow activity (theta) in the hippocampal EEG within 30 s. Similar effects were observed with BMY 7378 (20 and 100 μg/kg), which acts as an agonist at presynaptic (somatodendritic) 5-HT_1A receptors and as an antagonist at postsynaptic 5-HT_1A receptors. Power spectral analyses showed that all three compounds produced a dose-dependent 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 (relative theta power). The increase in relative theta power produced by 8-OH-DPAT (20 μg/kg) was greatly attenuated by spiperone (1 mg/kg), a highly effective 5-HT_1A autoreceptor antagonist. Administration of spiperone alone had no significant effect on relative theta power. These results are discussed in relationship to the effects of these drugs on serotonergic neuronal activity. Our results suggest that preferential activation of presynaptic 5-HT_1A receptors, and subsequent inhibition of serotonin neurotransmission, facilitates the appearance of hippocampal theta activity in awake cats.