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...
Fifteen rats were trained to discriminate between the tryptamine hallucinogen psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine; 1.0 mg/kg) and saline in a two-lever choice task. Dose-response and time-response curves were obtained. The psilocybin cue generalized to psilocin (the dephosphorylated congener of psilocybin) and to the prototypical indoleamine h...
Low intravenous doses of the hallucinogen d-lysergic acid diethylamide (LSD) markedly suppress the discharge of serotonin (5-HT)-containing neurons in the dorsal raphe nucleus of the rat. Microiontophoretically applied LSD also inhibits the firing of 5-HT neurons, indicating that the inhibitory effect is mediated directing on 5-HT neurons. Forebrain neurons ...
The hypothesis that the action of hallucinogenic drugs is mediated by a depression of the activity of brain serotonergic (raphe) neurons was tested by examining the behavioral effects of several hallucinogenic drugs while concurrently monitoring the activity of raphe neurons in freely moving cats. LSD produced a dose-dependent decrease in raphe unit activity...
In blood platelets of rabbits, the shape change-inducing effect of D-lysergic acid diethylamide (D-LSD) has been compared with the D-LSD-binding. D-LSD, but not L-LSD, caused a shape change reaction (EC50 1.3 x 10(-9) M) which was inhibited by various 5-HT antagonists (methergoline and neuroleptic drugs), butaclamol showing marked stereospecificity. Strong i...
Pigeons (N=4) were trained to discriminate between the effects induced by intramuscular (IM) injections of d-LSD and saline using a discrete-trial discrimination paradigm (choice between left and right hand key) in a conventional operant box. The solutions were administered IM15 min prior to the sessions. A FR15 schedule was in operation to produce food. Whi...
Three hallucinogens (d-lysergicacid diethylamide (LSD), mescaline, psilocybin) and two cannabinoid derivatives (tetrahydrocannabinol (THC), synhexyl) were tested for their long-term effects on the EEG of the cat. The drug-induced alterations in the EEG frequency spectrum were "drug-specific" in the sense that they would be statistically unlikely to occur dur...
The disruption of the temporal distribution of investigatory responses by rats in a novel hole-board following lysergic acid diethylamide-25 (LSD), as described in a companion paper (Geyer and Light, 1979), was found to be a characteristic effect of a variety of hallucinogens. Similar effects were produced by indoleamine hallucinogens, such as LSD, N,N-dimet...
Pairs of male Sprague-Dawley rats were administered mescaline, lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), 3,4-dimethoxyphenylethylamine (DMPEA), or 5-hydroxydopamine (5-OHDA) IP prior to being placed in a shock-elicited aggression situation. When foot shock was delivered, controls struck each other with their forepaws, but neve...
Tactile startle responding by male Sprague-Dawley rats given 60 presentations of air-puff stimuli (37.5 psi) was measured after the intraperitoneal administration of graded doses of hallucinogens and other psychoactive drugs. Among the drugs tested were the indoleamine-derived compounds, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine and psilocin, ...
The specific binding of 3H-serotonin to calf caudate homogenate was studied. The dissociation constant was 2nM and the number of specific sites was 14fmoles/mg protein. Of many drugs tested, inhibition of specific 3H-serotonin binding occurred almost exclusively with serotonin agonists and antagonists. The concentrations for 50% inhibition of 3H-serotonin bi...
The hallucinogenic indoleamine drugs N,N-dimethyltryptamine (N,N-DMT), psilocybin, bufotenin, 5-methoxy-N,N-dimethyltryptamine, and N-methyltryptamine, increased rat plasma prolactin (PRL) levels. The increase in plasma PRL produced by N,N-DMT, psilocybin, and bufotenin was inhibited by methysergide, a serotonin receptor blocker. Parachlorophenylalanine (PCP...
The effects of several indoleamines and phenethylamines were studied in the chronic spinal dog and compared with two standard drugs, LSD and amphetamine. In the nontolerant chronic spinal dog, their effects on a variety of physiologic and behavioral functions were measured in untreated dogs, as well as dogs treated with certain antagonists. The effects of th...
Using the micronucleus test as a screening method for mutagenic activity, no significant increase in the number of micronuclei was found when LSD, psilocybin or delta 9-THC were administered in 3 logarithmically increasing doses to mice, Azathioiprine (Imuran), given as a positive control, caused a statistically significantt increase in the micronucleated ce...
Two aspects of the complexities of the mode of action of drugs are described. One is the criteria and pitfalls of defining the interaction with specific receptors. The other is the need to consider each of the pharmacological effects of a drug as a concatenation of receptor events, because it has become clear that each drug may have substantial affinity for ...
In the course of examining the complete dose-response relationship for the behavioral effects of LSD in the cat, we discovered that, in addition to large increases in investigatory and hallucinatory-like responses, two behaviors, not previously reported, are emitted with a high probability under LSD. Beginning from a baseline of essentially zero in saline-tr...
The dopaminergic actions of various hallucinogenic drugs were assessed by examining their effects on turning behavior in rats with unilateral 6-hydroxydopamine lesions of the nigro-striatal pathway. LSD (0.1 and 0.2 mg/kg) produced strong contralateral turning, indicating that it is a potent dopamine receptor agonist, while BOL (5 mg/kg), a non-hallucinogeni...
