A Pharmacological Analysis of the Hyperactivity Syndrome Induced by Β‐phenylethylamine in the Mouse

Abstract

1 The effects of the putative 5-hydroxytryptamine (5-HT) receptor antagonists, methysergide, mianserin and methergoline, the dopamine receptor antagonists, haloperidol, thioridazine and clozapine, and the noradrenaline (NA) receptor antagonists, phentolamine, phenoxybenzamine and propranolol on the behavioural responses of mice to 3-phenylethylamine (PEA, 75 mg/kg) have been examined. 2 PEA produced a syndrome consisting of three distinct phases. The brief initial phase (0-5 min after injection) which consisted of forward walking, sniffing and headweaving, was succeeded by a locomotor depressant phase (5-20min after injection) which consisted of abortive grooming, headweaving, splayed hindlimbs, forepaw padding, sniffing and hyperreactivity, and a late locomotor stimulant phase (20-35min after injection), which was characterized by forward walking, sniffing, hyperreactivity, rearing and licking. 3 Methysergide, mianserin, methergoline, clozapine and propranolol inhibited headweaving and splayed hindlimbs, whereas haloperidol, thioridazine, phentolamine and phenoxybenzamine had no effect on these responses. Forepaw padding was strongly inhibited by methergoline and a high dose of mianserin, and weakly antagonized by methysergide, clozapine, haloperidol and thioridazine. In contrast, padding was mildly potentiated by phenoxybenzamine and phentolamine but strongly potentiated by propranolol. It is proposed that headweaving and splayed hindlimbs are 5-HT-mediated responses whereas forepaw padding also involves 5-HT mechanisms but may be partially due to release of tryptamine. 4 Rearing and licking were inhibited by haloperidol (most strongly), thioridazine and clozapine but potentiated by mianserin, methysergide, propranolol, phenoxybenzamine or phentolamine. Methergoline inhibited licking without affecting rearing. It is suggested that PEA-induced rearing and licking are produced by activation of dopaminergic neurones and inhibited by 5-HT or NA stimulation. 5 Phenoxybenzamine inhibited sniffing and produced backward walking when administered prior to PEA, suggesting mediation by NA of sniffing and an inhibitory influence of NA on backward walking. 6 Clozapine and thioridazine were the most effective antagonists of hyperreactivity and it is proposed that this response is dopamine-mediated. Forward walking was inhibited by high doses of haloperidol or clozapine and potentiated by methergoline, mianserin or methysergide, suggesting that hyperactivity may also be mediated by dopamine but subject to 5-HT inhibition. 7 Abortive grooming was the dominant behavioural component observed after PEA administration and was prevented by all of the antagonists tested which suggests that catecholamine and 5-HT mechanisms may be involved in the expression of this response. 8 Since PEA is an endogenous compound in animals and man, and has been claimed to be present in abnormal amounts in some schizophrenics, PEA-induced behavioural stimulation in mice (which includes the postulated hallucinogenic responses of abortive grooming and ...

Effects of beta-phenylethylamine on locomotor activity, body temperature and ethanol blood concentrations during acute ethanol intoxication

“…Our results have shown that PEA produced a monophasic stimulant effect per se and this response in rats differs from that seen in mice where an initial hypermotility, followed by depression then a secondary hypermotility, has been observed (Jackson 1972;Dourish 1982). The early stimulant phase in mice at least is thought to be dependent on intact pathways and receptors for DA and NA, while the late stimulation is due to a direct agonist action on post-synaptic dopamine receptors (Jackson 1975(Jackson , 1978.…”

Trace amine-associated receptor 1—Family archetype or iconoclast?

“…In rodents PEA elicits AMPH-like behavior (Hirano et al, 1989;Janssen et al, 1999) at doses of ∼50 mg/kg (intraperitoneal) characterized by hyperactivity, occasional walking backward, rearing, sniffing, gnawing, and licking (Dourish, 1982;Boulton, 1982;Lapin, 1996). At higher doses (75-100 mg/kg) repetitive, stereotypical behaviors, predominate including 'wet dog' shaking, excessive grooming and head movement, seizures, labored breathing, salivation, and straub tail.…”

“…Furthermore, pharmacologic manipulations (Borison et al, 1974;Borison et al, 1975;Boulton, 1976a;Philips & Boulton, 1979;Stoff et al, 1984;Boulton et al, 1990;Juorio et al 1991a;Juorio et al 1991b) and lesioning studies Juorio & Jones, 1981;Greenshaw et al, 1985;Greenshaw et al, 1986;Greenshaw et al, 1986;Juorio et al, 1987; can significantly influence TA turnover and levels with physiological (Becu-Villalobos, 1987;Cheng, 1990;Hirashima, 1999;Lee et al, 2003) and behavioral (Dourish, 1982;Lapin, 1996;Rex et al, 2004;Suo et al, 2006) consequences.…”

Dopamine transporter‐dependent and ‐independent actions of trace amine β‐phenylethylamine

“…In rodents, β‐PEA produces a robust behavioral phenotype consisting of short‐term stimulation of locomotor activity and stereotypy as well as a plethora of peripherally mediated effects (Dourish 1982; Boulton 1982; Saavedra 1989; Lapin 1996). Neurochemical characterization of this psychostimulant action leads to two major hypotheses.…”