Effect of hallucinogens on spontaneous and sensory-evoked locus coeruleus unit activity in the rat: reversal by selective 5-HT2 antagonists.
As previously reported, systemic administration of the hallucinogens D-lysergic acid diethylamide (LSD) (5-10 micrograms/kg) and mescaline (2 mg/kg) in the anesthetized rat produced a decrease in spontaneous activity but, paradoxically, facilitated activation of locus coeruleus (LC) neurons by sciatic nerve stimulation. In the present study, the hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) (20-80 micrograms/kg) was found to have similar effects. Systemic administration of the selective 5-HT2 antagonists LY 53857 (0.02-0.8 mg/kg) and ritanserin (0.1-0.3 mg/kg) completely reversed both actions of the hallucinogens on the LC. In contrast, LY 53857 did not reverse the effects of (+)-amphetamine (0.5 mg/kg) on the spontaneous or sensory-evoked activity of the LC. These results suggest that the common actions of indoleamine and phenethylamine hallucinogens displayed in the LC are mediated via 5-HT2 receptors; however, these receptors appear to be located outside the LC itself.
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology; D000818:Animals; D003913:Dextroamphetamine / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D006213:Hallucinogens / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000187:drug effects*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008635:Mescaline / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016713:Ritanserin
D004873:Ergolines; D006213:Hallucinogens; D010880:Piperidines; D016713:Ritanserin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D008238:Lysergic Acid Diethylamide; C032663:LY 53857; D008635:Mescaline; D003913:Dextroamphetamine