Serotonergic dorsal raphe neurons: subsensitivity to amphetamine with long-term treatment.

Rats were pretreated twice daily for six consecutive days with either saline or 1.0, 5.0, or 10.0 mg/kg (+)-amphetamine. On the following day, single-unit recording techniques were used to identify serotonin-containing neurons in the dorsal raphe nucleus (DRN). Pretreatment with amphetamine did not alter the mean spontaneous firing rate of these cells, but in some instances it appeared to produce periods of irregular bursting. Moreover, the response to challenge injections of amphetamine was reduced significantly by pretreatment with the large dose. Thus, whereas an intravenous challenge of approximately 3.0 mg/kg produced a greater than 50% inhibition of activity in the dorsal raphe nucleus in rats pretreated with saline, 1.0 or 5.0 mg/kg (+)-amphetamine, more than twice the challenge dose was required to suppress the activity of serotonergic neurons in rats pretreated with 10.0 mg/kg (+)-amphetamine. These results parallel those previously obtained with dopaminergic neurons, suggesting that both types of cells lose their sensitivity to amphetamine with repeated injections.