Buspirone affects hippocampal rhythmical slow activity through serotonin1A rather than dopamine D2 receptors.

Buspirone reduces anxiety clinically but, unlike classical anxiolytics, is not muscle relaxant, sedative, anticonvulsant or effective in increasing GABA function. The basis for its clinical action is not known, but action at both dopamine D2 and serotonin1A receptors has been suggested. Buspirone, like classical anxiolytics, produces a general reduction in the frequency of hippocampal rhythmical slow activity elicited by stimulation of the midbrain in the rat. Methysergide (3 mg/kg i.p.), GR38032F (0.3 mg/kg i.p.) and haloperidol (0.2 mg/kg and 2.0 mg/kg i.p.) failed to block this effect of buspirone (10 mg/kg i.p.). Apomorphine (0.3 mg/kg i.p.) had minor effects, but did not produce a general reduction in frequency. Pindolol (2 mg/kg i.p.) produced a small reduction in frequency itself. In the presence of pindolol, buspirone was without effect, while the effect of chlordiazepoxide (5 mg/kg i.p.) was potentiated. These results show that: (a) the similar effects of buspirone and classical anxiolytics such as chlordiazepoxide on reticular-elicited hippocampal rhythmical slow activity are achieved through different mechanisms; (b) the effects of buspirone in this particular test are more likely to depend on its interaction with serotonin1A receptors than its interaction with D2 receptors; and (c) that, as in other tests, buspirone does not act via serotonin2 or serotonin3 receptors.