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.
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004347:Drug Interactions; D006624:Hippocampus / Q000502:physiology; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D012653:Self Stimulation / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013681:Tegmentum Mesencephali / Q000502:physiology
D012702:Serotonin Antagonists; D000661:Amphetamine; D003913:Dextroamphetamine; D008784:Methysergide