In vivo electrophysiological techniques were used to study the effect of m-chlorophenylpiperazine, a non-selective serotonin-2C receptor agonist, on the activity of non-dopaminergic neurons in the substantia nigra pars reticulata and the ventral tegmental area of anesthetized rats. Intravenous administration of m-chlorophenylpiperazine (5-320 microg/kg) caused a dose-dependent increase in the basal firing rate of a subpopulation of nigral neurons which do not respond to a footpinch stimulus [P(0) neurons], whereas it did not affect the activity of neurons which are responsive to the footpinch [P(+) neurons]. However, m-chlorophenylpiperazine (5-320 microg/kg) excited all non-dopaminergic neurons sampled in the ventral tegmental area. Moreover, microiontophoretic application of m-chlorophenylpiperazine (10-40 nA) caused an excitation of P(0) nigral and ventral tegmental area neurons. Pretreatment with the selective serotonin-2C receptor antagonist SB 242084 (200 microg/kg, i.v.) completely blocked the excitatory effect of i.v. m-chlorophenylpiperazine (5-320 microg/kg), both in the substantia nigra pars reticulata and in the ventral tegmental area. It is concluded that stimulation of serotonin-2C receptors by m-chlorophenylpiperazine activates non-dopaminergic (presumably GABA-containing) neurons in the substantia nigra pars reticulata and ventral tegmental area.