5HT blockade and the stimulant effects of D- and L-amphetamine: no interaction in self-stimulation of prefrontal cortex, hypothalamus, or dorsal tegmentum. unexpected lethality in hippocampal sites.

We investigated the role of serotonin in the differential stimulatory effects of D- and L-amphetamine (1.0 mg/kg) on locomotor activity and on self-stimulation (SS) in rats. The serotonin antagonist methysergide (12.5 mg/kg) had no effects alone on activity or on SS. Methysergide enhanced the strong locomotor stimulatory effects of D-amphetamine and the weaker effects of L-amphetamine. D-amphetamine facilitated SS more strongly than L- in hypothalamic, dorsal tegmental, hippocampal and medial prefrontal cortical sites, but the effect of D-amphetamine was much weaker in prefrontal cortex than in other sites. Methysergide did not alter the effects of D- or L-amphetamine in any site except the hippocampus. Here, methysergide plus L-amphetamine suppressed SS; methysergide plus D-amphetamine suppressed SS in some rats and greatly increased it in others. When SS was facilitated by D-amphetamine plus methysergide, the combination was lethal. The possibility that lethality was due to adrenal crisis is discussed.