Differential effects of hallucinogenic drugs on the activity of serotonin-containing neurons in the nucleus centralis superior and nucleus raphe pallidus in freely moving cats

Abstract

Previous studies from our laboratory have demonstrated that there are a number of important dissociations between the effects of hallucinogenic drugs on the activity of serotonin-containing dorsal raphe neurons and behavior in freely moving cats. In the present study, we extended this analysis to serotonergic units in the nucleus centralis superior (NCS) and nucleus raphe pallidus (RPA). Lysergic acid diethylamide (LSD) produced a dose-dependent decrease in NCS unit activity at 10, 50 and 100 micrograms/kg (i.p.) and a dose-dependent increase in certain behaviors (e.g., limb flicking and abortive grooming) and the peak behavioral and unit changes were temporally correlated. By contrast, LSD had little effect on serotonin-containing RPA neurons. 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) also produced a dose-dependent decrease in NCS unit activity at 10, 50 and 250 micrograms/kg (i.m.) and dose-dependent behavioral changes. Similar to our LSD data, 5-MeODMT was found to have no overall significant effect on RPA unit activity, except at the highest dose level. Psilocin produced dose-dependent decreases in NCS unit activity at 25, 100 and 750 micrograms/kg (i.p.), whereas the behavioral changes were not dose-related. Psilocin also had relatively little effect on the activity of RPA neurons. The phenylethylamine hallucinogens, 2,5-dimethoxy-4-methylamphetamine (50, 250 and 1000 micrograms/kg i.p.) (DOM) and mescaline (5000 micrograms/kg i.p.), both produced large behavioral changes, but no overall significant effect on raphe unit activity in either the NCS or RPA. These data suggest that ascending dorsal raphe and NCS neurons may be involved in the process of hallucinogenesis, whereas descending RPA neurons do not appear to be involved in this process.(ABSTRACT TRUNCATED AT 250 WORDS)