This study examined the behavioral effects in rats of intracerebral administration of S(+)-3,4-methylenedioxymethamphetamine (S-MDMA) using an automated holeboard and open-field apparatus. Administration of S-MDMA into the nucleus accumbens septi produced locomotor hyperactivity. Although the stimulant effects of S-MDMA administered systemically are antagonized by fluoxetine pretreatment, the...
To investigate a possible basis for the proposed anti-addictive property of ibogaine, the effects of an ibogaine (40 mg/kg i.p.) pretreatment on in vivo neurochemical and motor effects induced by cocaine (20 mg/kg i.p.) were studied. Ibogaine, administered 19 h earlier, potentiated the increase in extracellular dopamine levels in striatum and nucleus accumbens as well as the stimulated motor...
Interpretation of the in vivo actions of 3,4-methylenedioxymethamphetamine (MDMA) is complicated by the formation of the active metabolite, 3,4-methylenedioxyamphetamine (MDA). This study evaluates the role of MDA in the dopamine releasing actions of (+)-MDMA. In the study, rats were given subcutaneous doses of (+)-MDMA and concentrations of monoamines and their metabolites in striatal...
Ibogaine, an indolalkylamine, has been claimed to be effective in abolishing drug craving in heroin and cocaine addicts. The present study used in vivo microdialysis to determine the effects of ibogaine on extracellular levels of dopamine (DA) and its metabolites and the effects of ibogaine pretreatment on morphine stimulation of brain DA systems. Acutely, ibogaine (40 mg/kg i.p.) decreased...
Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addition to opiate and stimulant drugs. As a preclinical test of this claim, the present study sought to determine if ibogaine would reduce the intravenous self-administration of morphine in rats. Ibogaine dose dependently (2.5-80 mg/kg) decreased morphine intake in the hour after ibogaine treatment (acute...
This study examined the [3H]5-HT-releasing properties of 3,4-methylenedioxymethamphetamine (MDMA) and related agents, all of which cause significant release of [3H]5-HT from rat brain synaptosomes. 5-HT uptake blockers dose dependently block MDMA-induced [3H]5-HT release. The EC50s of the uptake drugs in blocking MDMA-induced release correlate with their affinity for the 5-HT uptake site...
Rats immobilized for 2 h daily for 7 days showed an increased behavioral response (forepaw treading and hind-limb abduction) to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) 24 h after the last stress session. An injection of naloxone before each stress session fully antagonized the increased behavioral reactivity to 5-MeODMT. Treatment with morphine or beta-endorphin associated with each...
In order to further evaluate the extent to which particular 5-HT receptor subtypes (5-HT1, 5-HT2) might be involved in the behavioral effects of hallucinogenic drugs, rats were trained to discriminate mescaline (10 mg/kg i.p.) from saline and were given substitution (generalization) and combination (antagonism) tests with putatively selective serotonergic and related neuroactive compounds. The...
The effects of four benzodiazepines (diazepam, clonazepam, oxazepam and clobazam) were studied on the head-twitch response induced in mice by several 5-HT receptor agonists. All the benzodiazepines tested potentiated the effects of the directly acting agonists 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine and mescaline, without themselves inducing head-twitches. In contrast, none of...
5-HT induced an increase in blood pressure in the pithed rat which was antagonized by LY 53857 a selective 5-HT2 receptor antagonist. It was not antagonized by spiroxatrine, MDL 72222, idazoxan or AR-C 239, respectively 5-HT1-like and 5-HT3 receptor antagonists, alpha 2- and alpha 1-adrenoceptor antagonists. 5-MeODMT also induced an increase in blood pressure which was antagonized by LY 53857...
Twenty-one indolealkylamines, some of which are known to be psychoactive in man, were examined for their binding interactions with rat brain cortical 5-HT2 receptors labeled with the antagonist radioligand [3H]ketanserin in order to develop structure-activity relationships for binding at these sites. Features investigated included aromatic, alpha-methyl and terminal amine substituents....
The present experiments served to compare the effects of the 3 5-HT1 agonists, 8-OH-DPAT, 5-MeODMT and TFMPP on the blood pressure and heart rate of normotensive anaesthetized rats. All the agonists induced, after i.v. injection, a decrease in blood pressure and heart rate. The hypotensive effects of 5-MeODMT and TFMPP were preceded by an increase, suppressed by both ketanserin and...
Ritanserin (0.125, 0.25, 0.5, 1.0 and 2.0 mg/kg s.c.), a selective serotonin (5-HT2) receptor antagonist, produced a dose-dependent inhibition of the head-twitch response induced in mice by phencyclidine (PCP) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). In contrast, ritanserin, dose dependently increased PCP- and 5-MeODMT-induced head-weaving. There was a significant inverse relationship...
In rats treated with phencyclidine (PCP) repeatedly (PCP 10 mg/kg per day for 14 days), the back-pedalling, head-weaving and turning induced by PCP were attenuated (tolerance), while PCP-induced sniffing, rearing and ambulation were potentiated (supersensitivity). The behavior induced by the direct and indirect serotonin (5-HT) agonists, 5-methoxy-N,N-dimethyltryptamine and p-chloroamphetamine,...
This study was designed to assess whether phencyclidine (PCP)-induced behaviors in rats were potentiated after two days' withdrawal from chronic methysergide (a 5-HT2 receptor blocker) treatment (10 mg/kg per day i.p. for 12 days), in order to confirm the involvement of 5-hydroxytryptamine (5-HT) neurons in PCP actions. The PCP (10 mg/kg)-induced behaviors (head-twitch, head-weaving, turning...
The rank order of potency for the physiological effects of three phenethylamine hallucinogens in the locus coeruleus (LC) was identical to that previously shown for their 5-HT2 binding affinity [-) DOB greater than DOM greater than ( + )DOB). The behaviorally inactive positional isomer of DOB, SL-7161, did not significantly affect LC unit activity. These results offer insight into...
We compared the effects of the hallucinogens 2,5-dimethoxy-4-methylamphetamine (DOM), mescaline and the simulant D-amphetamine, applied by microiontophoresis to rat dorsal raphe (DR) units. DR neuron firing rate was relatively insensitive to DOM and unaffected by mescaline, but was clearly inhibited by D-amphetamine. Intravenous DOM usually inhibited, but this effect was correlated with blood...
The 5-HT receptor subtypes involved in the mediation of reciprocal forepaw treading and the flat body posture induced by the central 5-HT receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), were examined in intact rats and in rats depleted of monoamines with reserpine. Forepaw treading in non-reserpinised rats was antagonised by the 5-HT2 receptor antagonist, ketanserin, only at...
Chronic administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 2 mg/kg i.p., every 30 min for 4 h) produced a dramatic tolerance to the behavioral effects of the drug in rats. The ED50 for the syndrome-inducing effects of the drug was increased from 1.3 to 2.4 mg/kg, and the mean duration of the syndrome was decreased from 14.9 to 1.2 min after this treatment. This tolerance effect...
The discriminative stimulus properties of nitrous oxide, an analgesic and anesthetic gas, were evaluated in rats trained to discriminate the effects of morphine or ethylketocyclazocine. Administration of nitrous oxide in concentrations as high as 80 percent did not produce generalization to the discriminative cue produced by morphine. Nitrous oxide did, however, generalize in a...
Chemical lesioning of the 5-hydroxytryptamine neurones in the brain with 5,7-dihydroxytryptamine (200 micrograms i.c.v., 14 or 21 days previously) resulted in an enhanced behavioral response following administration of the 5-hydroxytryptamine receptor agonist 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg). The increase in the behavioural response showed a positive correlation with the decrease in...
Specific binding of [3H]lysergic acid diethylamide (LSD) to human platelet membranes, as defined by 300 nM spiperone, was saturable over the concentration range of 0.25-2.5 nM [3H]LSD. At 0.5 nM [3H]LSD the half-time for association at 37 degrees C was 56 min, half-time for dissociation was 173 min, and the kinetically derived affinity was 0.24 nM. In 19 control subjects equilibrium binding...
The characteristic behavioral effects of mescaline in cats were nearly completely blocked by pretreatment with low doses of either a specific serotonin antagonist (methysergide) or a dopamine specific antagonist (haloperidol). These blocking effects were not due to non-specific actions, since methysergide did not block the behavioral effects of apomorphine, and haloperidol did not block the...
The effects of 5-MeODMT (2.5 mg/kg), diazepam (1 mg/kg), methysergide and the stereoisomers of propranolol (6 mg/kg) on hyponeophagia were studied in both sexes of the Roman strains of rats, selectively bred for acquisition of a two-way conditioned avoidance response. Diazepam, methysergide and 1-propranolol increased feeding in a novel environment whilst 5-MeODMT decreased it and d-propranolol...
In superfusion experiments with a crude synaptosomal fraction from the nucleus accumbens of rats, lysergic acid diethylamide, mescaline and N,N-dimethyltryptamine (representing different chemical classes of psychotomimetics) produced a concentration-related inhibition of K+-evoked [3H]dopamine release whereas spontaneous release remained unchanged. The nonpsychotomimetic ergoline lisuride...