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PubMed1989

Effects of intraocular mescaline and LSD on visual-evoked responses in the rat.

The effects of mescaline and LSD on the flash-evoked cortical potential (FEP) were determined in unrestrained rats with chronically-implanted electrodes. Systemic administration of mescaline or LSD significantly attenuated the primary component of the FEP at three stimulus intensities with the greatest effect observed 60-90 minutes following drug administration. The magnitude and specificity of the effects of these agents on the primary response suggest that they produce deficits in conduction through the retino-geniculato-cortical system. The serotonin receptor antagonists, cyproheptadine and methysergide, antagonized the mescaline-induced depression of the FEP in accordance with neurochemical and behavioral evidence that mescaline acts as a partial agonist on serotonin receptors. Topical or intraocular administration of atropine antagonized the actions of systemically-administered mescaline. In addition, intraocular administration of mescaline or LSD attenuated the FEP indicative of an action of these hallucinogens on visual processing in the retina which is modulated by muscarinic receptor activity.

Administration, Topical↗
PubMed1986

Mescaline action on "memory decay" and "problem solving" behavior in the rat.

The modifications of behavior caused in the rat by a chronic oral administration of mescaline have been studied in three experimental situations. In the staircase maze mescaline accelerated the spontaneous decay on the conditioned reflex (memory decay) during the period without daily training. Only the results observed at 30 mg/kg/day of mescaline were statistically significant. In a T maze two lateral alleys closed by two swinging doors, 30 mg/kg/day of mescaline increased the time spent in opening the first door. When the two doors of the lateral alleys were closed with a latch, mescaline 30 mg/kg/day, caused an increase in the time spent by the rat in opening the doors. Mescaline caused an increase in food consumption. The increase at 30 mg/kg/day is statistically significant.

Administration, Oral↗
PubMed1998

Blood flow and cerebral laterality in the mescaline model of psychosis.

The psychological, neuropsychological, and neurometabolic effects of the hallucinogenic agent mescaline were investigated in 12 normal male volunteers. Between 3 1/2 and 4 hours after drug intake, mescaline produced an acute psychotomimetic state, as measured by the BPRS and PDS-P. The APZ questionnaire revealed the specific effects of mescaline in the visual system. Neuropsychological effects were studied with a face/non-face decision task with known right hemisphere advantage, in which mescaline induced a decrease in functioning of the right hemisphere. In functional brain imaging using SPECT, mescaline produced a "hyperfrontal" pattern with an emphasis on the right hemisphere, which was correlated with mescaline-induced psychotomimetic psychopathology. Our findings question the validity of the concept of hypofrontality as an explanation for acute psychotic symptomatology.

Adult↗
PubMed1975

A comparison of the effect of mescaline on activity and emotional defaecation in seven strains of mice.

1 Mescaline hemi-sulphate (35 mg/kg body weight) was injected intraperitoneally into male mice (Mus musculus) from seven genetically diverse laboratory strains. 2 The effect of mescaline was found by comparison of the emotional defaecation and open field activity of mice after mescaline injection with the performance of the same mice after a subsequent saline (0.9% w/v NaCl solution) control injection. 3 In strains A2G, C3H/He, C57BR/cd, CBA/Cam and F/St, mescaline inhibited emotional defaecation and stimulated open field activity. These effects did not occur in strains 1CFW and Schneider. 4 A positive relationship was found between the degree of emotional defaecation characteristic of each strain in the saline control experiment and the inhibitory effect of mescaline on emotional defaecation. 5 Pre-treatment of mice with tranylcypromine (20 mg/kg body weight, i.p.) had no effect on emotional defaecation or on its inhibition by mescaline.

Animals↗
PubMed1975

Studies on accumulation of (14C)-mescaline in brain homogenates: effects of psychotropic and other agents.

Incubation of rat brain homogenates or 14,500 g pellet isolated from the homogenate with (14C)-mescaline was associated with accumulation of (14C)-mescaline in the pellet. 1.33 mumol/ml of chlorpromazine, trifluoperazine, fluphenazine, imipramine, desmethylimipramine, nortriptyline and amitriptyline inhibited the accumulation of mescaline. Lower concentrations (0.133-0.44 mumol/ml) of the psychotropic drugs were less effective. The tricyclic antidepressants were less potent than the tranquilizers. Although the trimethoxyphenylacetic acid (TMPA) levels of the pellet were also reduced by the psychotropic drugs, the TMPA:mescaline ratios were unchanged indicating that the drugs had no effect on the metabolism of mescaline. The inhibition of accumulation of mescaline by the high concentrations of tranquilizers may divert more of the hallucinogen to the receptor site. Thus, an explanation for the reported worsening of clinical syndrome of hallucinogenic poisoning by tranquilizers is provided.

Animals↗
PubMed1976

Development of tolerance to the antinociceptive effect of mescaline intraventricularly administered to rabbits.

Some effects of intraventricular injection of mescaline are examined in conscious rabbits. By means of electrical stimulation of the tooth pulp it is shown that an acute treatment with 70, 100, 150 mug/kg of mescaline elicits analgesia, the intensity of which is dose-dependent: with daily administration of 100 mug/kg for 5 days a complete tolerance develops to the antinociceptive effect. A tolerance also develops to the behavioral effects of mescaline after repeated administrations, with the exception of the stuporous state, a symptom which, on the contrary, is accentuated as the treatment proceeds. An EEG arousal is induced in the rabbit by acutely administered mescaline; the chronic treatment (100 mug/kg) makes the return of voltage to original levels progressively slower. Finally, the confrontation of certain of the mescaline-induced effects with those of morphine suggests some biochemical and neural patterns common to the 2 drugs.

Analgesia↗
PubMed1971

Effect of mescaline on single cortical neurones.

The effects of mescaline upon single cortical neurones were studied, using the microiontophoretic technique. Mescaline elicited excitatory and depressant responses similar to those evoked by noradrenaline (NA) and 5-hydroxytryptamine (5-HI). The responses to NA and mescaline were usually in the same direction, the neurone being either excited by both drugs or depressed by both drugs. The correlation between the effects of mescaline and 5-HT, however, was less consistent. The beta-adrenoceptor blocking agent MJ-1999 and the 5-HT antagonist methysergide were both effective in antagonizing mescaline responses.

Adrenergic beta-Antagonists↗
PubMed1975

Blockade of the stimulus properties of mescaline by a serotonin antagonist.

It is known that the effects of mescaline (3, 4, 5-trimethoxyphenylethylamine), a hallucinogen, can function as a discriminative stimulus. The present investigation examined the ability of cinanserin, a serotinin antagonist, to block the stimulus properties of mescaline in the rat. After a reliable discrimination was established between the effects following the injection of mescaline (10 mg/kg) and those following administration of saline, subjects were pretreated with cinanserin HC1 (3 mg/kg) and then treated with mescaline. Such pretreatment was found to block discrimination, i.e., the response rate following the administration of mescaline plus cinanserin was appropriate for the saline condition. The present data suggest that antagonists of serotonin may be useful in furthering our understanding of phenethylamine hallucinogens.

Animals↗
PubMed1975

Interaction of mescaline with phenothiazines: effect on behavior, body temperature, and tissue levels of hallucinogen in mice.

Mescaline (25 mg/kg; 66 muc/kg) was injected (ip) in mice 45 min before chlorpromazine (CPZ, 2.5, 5, 15 mg/kg), thioridazine (10, 30, 45 mg/kg), or chlorpromazine-sulfoxide (CPZ-SO, 15 mg/kg). Excitement, agitation, slight increase in ventilation and occasional head-shaking were seen 30 min after mescaline and continued for 30-45 min thereafter; locomotor activity and the number of scratching events were significantly increased during this period. CPZ (2.5, 5, 15 mg/kg) and thioridazine (10, 30, 45 mg/kg) partially or completely blocked mescaline-induced gross behavior; CPZ-SO (15 mg/kg) was not effective. Increased scratching responses and locomotor activity induced by mescaline were antagonized by all doses of CPZ and thioridazine; at higher doses, both CPZ (7.5, 15 mg/kg) and thioridazine (45 mg/kg) induced cataleptic-like condition and marked hypothermia. Tissue levels of mescaline, examined 3 hr after its administration, were increased by all doses of CPZ and a higher dose of thioridazine (45 mg/kg); CPZ-SO and lower doses of thioridazine had no effect.

Animals↗
PubMedDate not supplied

Cactus alkaloids. XXXVI. Mescaline and related compounds from Trichocereus peruvianus.

Agurell has previously detected (tlc, glc-ms) tyramine, 3-methoxytyramine, and two unknown alkaloids in the Peruvian cactus, Trichocereus peruvianus Br. and R. The presence of mescaline in other similar Trichocereus species prompted us to reinvestigate this species, which is commercially available in the United States. The nonphenolic alkaloid extracts yielded an abundance of crystalline mescaline hydrochloride (0.82% yield) and a trace of 3,4-dimethoxyphenethylamine (tlc-ms). Crystalline tyramine hydrochloride, 3-methoxytyramine hydrochloride, and 3,5 dimethoxy-4-hydroxphenethylamine hydrochloride were isolated from the phenolic alkaloid extracts; the last compound has not been previously crystallized from nature, although it is the immediate biosynthetic precursor of mescaline. Crystalline 2-chloromescaline hydrochloride was isolated drom the nonphenolic extracts; but, as determined by mass-analyzed ion kinetic energy spectrometry, this new compound is an extraction artifact. Both 2-chloromescaline and 2.6-dichloromescaline hydrochlorides were prepared synthetically from mescaline. This cactus species has a mescaline content equal or superior to peyote and should be legally controlled as an item of drug abuse.

Chemical Phenomena↗
PubMed1979

Effects of mescaline and amphetamine on simultaneous visual discrimination in two inbred strains of mice.

The effects of mescaline and amphetamine were investigated in BALB/cJ (BALB) and C57BL/6J (C57) mice using the five-choice Yerkes--Thompson Bryant--Bovet-Nitti apparatus for patterns discrimination. Two sets of experiments were carried out. In the first set, pretrial administration of mescaline (5, 10, and 20 mg/kg) was followed by performance improvements in the C57 mice, while performances of the BALB strain were impaired by the treatment, as compared with those of the saline-injected (4 ml/kg) controls. The pretrial administration of amphetamine (0.1, 0.25, and 0.5 mg/kg) improved performances of both strains. In a second set of experiments, the same effects as in the pretrial experiments were observed in both strains following administration of mescaline (20 mg/kg) and amphetamine (0.5 mg/kg) immediately after each experimental session. No effect was evident when the drugs were injected 2 h after training, suggesting that effects of the pretrial treatments were due to influences of mescaline and amphetamine on the consolidation processes of the two strains of mice tested.

Animals↗
PubMed1979

Severe aggression in rats induced by mescaline but not other hallucinogens.

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 never engaged in either biting or injurious fighting. Mescaline-treated rats (50 or 250 mg) rarely struck each other, but engaged in nearly lethal biting. While LSD (25--400 micrograms/kg), psilocin (2.0 mg/kg), and DMT (5 mg/kg) produced some biting, this did not significantly differ from controls and never resulted in injuries. At higher doses, psilocin, DMT, and DMPEA decreased the amount and intensity of fighting. Rats treated with 5-OHDA (8--200 mg/kg) or LSD (25--400 micrograms/kg) did not differ from controls. These results suggest that mescaline's ability to induce pathological aggression in rats exposed to foot shock is not shared by other hallucinogens or nonhallucinogenic mescaline analogues.

Aggression↗
PubMed1975

Electroencephalographic studies on the development of tolerance and cross tolerance to mescaline in the rat.

Recordings of the electroencephalogram (EEG) and the electromyogram (EMG) were collected continuously from rats equipped with permanent cortical and temporalis muscle electrodes. Automatic injections of mescaline were administered through indwelling i.p. cannulas at an initial dose of 30 mg/kg every 6 hrs for the first 2 days. This dose was then increased to 60 mg/kg 6 hr which was given for the duration of the study. The initial injections of the mescaline induced an immediate desynchronization of the EEG and behavioral arousal of the rat, which endured for 2-3 hrs. After this time, slow wave (SW) sleep and rapid eye movement (REM) sleep episodes reappeared, with the return of regular alternations of the sleep-wakefulness cycle. Upon continued administration of the drug, partial tolerance to the arousal effects of mescaline developed, which was reflected by a gradual reduction in the latencies to onset of SW sleep and REM sleep. Rats rendered tolerant to mescaline in this manner were found to be cross tolerant to lysergic acid diethylamide (LSD) and N,N-diethyl-tryptamine (DET). In contrast, cross tolerance did not occur to amphetamine, which exerts similar arousal and EEG desynchronizing effects. These results agree with physiological and behavioral studies of tolerance and cross tolerance among hallucinogens and support the usefulness of the EEG as a quantitative indicator of central nervous system function.

Amphetamine↗
PubMed1977

Facilitation and disruption by mescaline and 3,4-dimethoxyphenylethylamine of shock avoidance in rats.

The effects of mescaline hydrochloride (4.95-79.2 mg/kg i.p.) and its non-hallucinogenic analogue 3,4-dimethoxyphenylethylamine hydrochloride (DMPEA) (12.5-100 mg/kg i.p.) on shock avoidance in a shuttlebox were studied in male Long-Evans rats trained to high (above 88%, good performers) or low (below 6%, poor performers) stable base-line avoidance rates. In good performers, mescaline and DMPEA caused a dose-dependent decrease in avoidance rate (ED 50's 44.6 and 39.2 mg/kg, respectively) without affecting presession (5-min adaptation period) or intertrial shuttlebox crossings. In poor performers, mescaline caused a dose-dependent increase in avoidance rate (ED 50 = 24.8 mg/kg) and intertrial crossings, without affecting presession crossings. The results suggest that mescaline, but not DMPEA, has dual facilitative and disruptive effects on avoidance behavior at similar dose ranges. The facilitative, but not the disruptive, effect may be related to changes in motor activity.

Animals↗
PubMed1976

Mescaline: its effects on learning rate and dopamine metabolism in goldfish (Carassius auratus).

The pharmacological action of mescaline on goldfish was studied with the Bitterman-Agranoff shock-avoidance test. In short term experiments with high mescaline doses an increase in learning rates was observed. Similar results were obtained with apomorphine and L-dopa. However, when the fish were exposed to smaller mescaline doses (or to fluphenazine) for 3 days, their ability to avoid electric shock was reduced. Apparently, mescaline induced a release of dopamine which stimulated central dopaminergic systems. Subsequently, MAO destroys the liberated dopamine. Thus, the ensuing dopamine deficit appears to be responsible for the marked changes in behavior in the chronic experiment.

Animals↗
PubMedDate not supplied

Effect of clozapine and molindone on plasma and brain levels of mescaline in mice.

Levels of unchanged mescaline were examined in the plasma and brain of albino Swiss-Webster mice pretreated with various doses of either clozapine or molindone. In clozapine treated mice, the mescaline levels were statistically significantly higher at 2 and 3 h with 7.5 and 15.0 mg/kg and at 1, 2 and 3 h with 30 mg/kg. Molindone at 4.0 and 8.0 mg/kg produced no significant effect; at 16.0 and 48.0 mg/kg, the levels were significantly higher at 1 and 2 h. Elevated brain levels of mescaline by clozapine and molindone indicate an adverse metabolic interaction between a hallucinogen and drugs that are commonly used to treat mescaline-induced psychosis.

Animals↗
PubMed1989

Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline.

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 mescaline cue generalized to relatively high doses of the 5-HT2 agonists, 2,5-dimethoxy-4-methylamphetamine (DOM), LSD and psilocybin; the extent of generalization to 5-HT1 agonists (8-hydroxy-2-[diethylamino]tetralin (8-OHDPAT), RU-24969 and 8-hydroxy-2-[di-n-propylamino]tetralin (TFMPP] was unclear. Combinations of the training drug and sufficiently high doses of 5-HT2 antagonists (ketanserin, LY-53857, pirenperone) were followed by saline-lever responding; less selective central 5-HT (metergoline), and DA (SCH-23390, haloperidol) antagonists, did not block the mescaline cue. These data suggest that 5-HT2 receptors are involved in the stimulus properties of mescaline.

Animals↗
PubMed1979

Mescaline increases startle responding equally in normal and raphe-lesioned rats.

To test the possible involvement of serotonin-containing cells of the midbrain in mediating the effects of mescaline on startle responding, electrolytic lesions were made in either the dorsal or median raphe nucleus in rats. Decreases in either striatal or hippocampal tryptophan hydroxylase activity confirmed the effectiveness of the lesions. One week later, startle was measured in response to 30 air-puff stimuli for each rat. Median, but not dorsal, raphe lesions increased startle magnitudes throughout the test session. The following day each group was divided into matched halves and were given 60 trials, 30 minutes after intraperitoneal injection of either saline or 10 mg/kg mescaline. Despite the large differences in baseline startle among the groups, mescaline produced comparable 25% increases in startle magnitudes in both sham- and raphe-lesioned animals. This result fails to support the hypothesis that increased startle responding produced by mescaline is mediated by the midbrain raphe nuclei.

Animals↗