Inhibition by 8-hydroxy-2-(di-n-propylamino) tetralin and SM-3997, a novel anxiolytic drug, of the hippocampal rhythmical slow activity mediated by 5-hydroxytryptamine1A receptors.

Electrophysiological studies using spectral analysis techniques were undertaken in rabbits to determine whether or not hippocampal rhythmical slow activity (RSA, theta wave activity) was affected by the 5-hydroxy-tryptamine1A (5-HT1A) agonists 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) and 3a alpha, 4 beta, 7 beta, 7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-4, 7-methano-1H-isoindole-1,3(2H)-dione dihydrogen citrate (SM-3997, a newly synthesized anxiolytic drug). Intravenous administration of 8-OH-DPAT and SM-3997 induced a desynchronized pattern with low-amplitude slow wave activity in the hippocampal EEG and inhibited RSA generation following stimulation of the midbrain reticular formation. RSA was also inhibited by 5-HT1A related anxiolytics such as buspirone, gepirone, and ipsapirone. The effects of 8-OH-DPAT and SM-3997 on the hippocampal RSA were blocked by pindolol, which has 5-HT1A antagonistic activity. Direct microinjection of these 5-HT1A selective agonists into the hippocampus inhibited generation of the hippocampal RSA. These findings indicated that 8-OH-DPAT and SM-3997 inhibited the hippocampal RSA by acting on hippocampal 5-HT1A receptors.