Neuroleptics attenuate stereotyped behavior induced by beta-phenylethylamine in rats

\u3b2-phenylethylamine (PEA), a sympathomimetic amine, has been detected in a number of mammalian tissues (Wyatt et al., 1977), but its function is unknown. It is structurally similar to amphetamine; the only difference being the absence of a methyl group on the \u3b1-carbon of the side chain. PEA is preferentially degraded by the type B (Yang and Neff, 1973) monoamine oxidase (MAO) which is deficient in the platelets of some chronic schizophrenics (Wyatt and Murphy, 1976). PEA, like amphetamine, produces stereotyped behavior and hyperactivity in rats (Randrup and Munkvad, 1966; Sabelli et al., 1975); moreover, there are progressive increases in these behaviors with increasing dosages of both PEA and the monoamine oxidase inhibitor (MAOI), pargyline (Moja et al., 1976). In this paper we report modification of PEA-induced stereotyped behavior (in pargyline-pretreated rats) by neuroleptic drugs. Pargyline, when given in the doses used here, preferentially inhibits the B form of MAO (Fuentes and Neff, 1975)

Dose response and time course effects off N,N-dimethyltryptamine on dissruption of rat shuttlebox avoidance

N,N-Dimethyltryptamine (DMT) was given (ip) in different doses (0.25, 0.5, 1.0, 2.0, 4.0, 8.0 mg/kg) in a randomized order to a group of ten rats (Fisher 344/Mai) who were trained to a high, stable base line of conditioned avoidance responding in the shuttlebox. DMT produced dose-dependent disruptive effects, as a sigmoid function, with 1.0 mg/kg the minimal dose causing disruption and progressively more disruption with increasing doses, reaching a plateau at the highest dose. The disruptive effects were time-related, with onset and peak 8 min after injection, gradual decline thereafter, and disappearance by about 25-30 min. Both the threshold dose and time course for the disruptive effects correspond closely to what has been previously reported for DMT's psychological effects in humans

Dose-response effects of beta-phenylethylamine on stereotyped behavior in pargyline pretreated rats

We studied the dose-response and the time-course effect of beta-phenylethylamine (4.0-64.0 mg/kg, ip) on stereotyped behavior and motor activity in male Sprague-Dawley rats pretreated 2 hr eariler with pargyline (0.25-8.0 mg/kg, iv). Stereotyped behavior, defined as repetitive, nongoal-directed head movements and sniffing, and changes in motor activity were observed immediately after injection of beta-phenylethylamine for a 1 hr period. With increasing doses of pargyline pretreatment, beta-phenylethylamine produced, in a dose-response relationship, progressively more stereotyped behavior accompanied by increased motor activity. Without pargyline pretreatment, only 64.0 mg/kg beta-phenylethylamine induced behavioral changes. Stereotyped behavior and increased motor activity had an onset at 4-6 min after the injection of beta-phenylethylamine, peak at 10-30 min, and gradual decline in the next 10-20 min. These results are discussed in terms of a possible relationship with the degree of inhibition of Type a and Type B monoamine oxidase acused by the different doses of pargyline

Testosterone-attenuated sterotypy and hyperactivity induced by beta-phenylethylamine in pargyline-pretreated rats

Testosterone pretreatment (1.0-4.0 mg/kg) attenuated, in a dose-response fashion, the induction of stereotyped behavior and hyperactivity by pargyline (0.25, 4.0 mg/kg) and beta-phenylethylamine (8.0, 16.0 mg/kg) in preubertal, male rats. The dyskinetic movements induced by pargyline and beta-phenylethylamine were proposed as a possible animal model for tardive dyskinesias. Attenuation by testosterone of these effects suggested an hormonal involvement consistent with the reported predominant occurrence of tardive dyskinesias in women and in the elderly

Reduction of REM-sleep by a tryptophan-free amino acid diet

The acute administration of a tryptophan-free amino acid diet to rats has previously been reported to produce a marked reduction in brain serotonin concentrations. The present study examined the effects of such a diet on electroencephalographic sleep measures. There was a decrease in REM sleep and a small increase in nonREM sleep, with no change in total sleep time. In view of these and other observations, the hypothesis that the serotonergic system plays an important role in the maintenance of nonREM sleep should be carefully reevaluated

Tolerance development to a disruptive effect of beta-phenylethylamine (PEA) on a learned behavior in rats

Several doses (8-64 mg/kg) of \u3b2-phenylethylamine (PEA), a naturally-occurring sympathomimetic amine structurally related to amphetamine and with similar effects on animal behavior, were administered (IP, daily for ten days) to Fisher 344 rats that were trained to perform a shuttlebox conditioned avoidance response (CAR) at a high, stable rate. PEA 8 mg/kg did not influence avoidance responding after single or multiple injections. Acute administration of PEA 16 mg/kg produced dose-dependent disruptions of the CAR. With repeated administration, complete tolerance to CAR disruption was acquired by the third injection of PEA 16 mg/kg or by the fifth injection of PEA 32 mg/kg and maintained with both doses through ten injections; the use of appropriate controls indicated that tolerance was pharmacological and not behavioral. Over the course of ten injections, tolerance did not develop to shuttlebox disruption caused by 64 mg/kg, and this dose of PEA did not elicit tolerance to stereotyped behavior after 21 injections. These data were interpreted as showing differential tolerance to low vs. high dose effects of PEA: Lower doses produce tolerance to disruption of the CAR, but the highest dose did not because of the presence of incompatible response tendencies (e.g., stereotypy) interfering with the CAR. Our data showing development of tolerance to lower doses of PEA is the first demonstration in the literature that tolerance can develop to a behavioral effect of this compound

Decrease in plasma tryptophan after tryptophan-free amino acid mixtures in man

Male healthy subjects, fasting 12 hours, ingested increasing amounts of a mixture containing a fixed proportion of seven essential amino acids (l-isoleucine 11.5%, L-leucine 18.0%, L-lysine 13.1%, L-methionine 18.0%, L-phenylalanine 18.0%, L-threonine 8.2%, L-valine 13.1%) and lacking tryptophan. The diets produced a rapid fall in plasma tryptophan which was proportional to the total amount of the amino acids ingested. Following the highest dose administered (36.6 g) plasma tryptophan fell to a minimum of about 35% the initial level and remained markedly reduced at 6 hours after treatment. The mechanism of this decrease and its potential clinical relevance are discussed