Bog. Nemo-PqphophrmnacoZ. Vo1.2, pp. 425-430, 1978.Pergamon Press Ltd. Printed in Great Britain. NALOXONE BLOCKS AWPRgTAWINB-INDUCKD RRARING: POTENTIAL INTERACTION BRTWKgN CATECWOLAMINRS AND ENDCRPHINS SUZANNE RABEB, TOM RATSUKAWI, PHILIP A. BERGRR, JACK D. BARCEAS and RlJDA AKIL Nancy Pritzker Laboratory of Behavioral Neurochemistry Department of Psychiatry and Behavioral Sciences Stanford University School of Medicine Stanford, CA., U.S.A. (Final form, July 1978) Abstract 1. The effect of 10 mg/kg of naloxone on amphetamine- (1.5 mg/kg) induced behavior was evaluated. 2. Naloxone did not alter amphetamine-induced hyperactivity or stereotypy, but did selectively block rearing behavior. 3. This effect raises two interesting issues: a) It suggests that the first phase of amphetamine-induced behavior in rats (hypermotility) might be considered as having two subcomponents modulated by different mechanisms; b) It adds support to an already growing literature on possible catecholamine-endorphin interactions. Keywords: Naloxone, amphetamine, hypermotility, stereotypy, rearing, catecholsmine- endorphin interactions Introduction In recent years, a flurry of experiments has focused on the endogenous opiate-like peptides and their antagonists. Particular attention has been paid to their possible role as neuroregulators and their behavioral function. Naloxone, an opiate antagonist, produces rapid reversal of opiate action, eliciting almost immediate withdrawal; yet laboratory studies show very few behavioral effects of the drug when tested alone. Hcwever, when used with other pharmacological agents (not necessarily opiates), naloxone does appear to modu- late behavior. Harris et al. (1977) reported that naloxone potentiated the effects of apaaorphine, and ET-495 on fixed-interval schedule of food presentation. Naloxone by itself did not affect this behavior. Furthermore, a decrease in amphetamine-induced avoidance responding and locomotion by naloxone was reported by Holsman (1974). We were interested in further exploring possible effects of naloxone on amphetamine-induced behavior. In particular, we wanted to know whether naloxone blocked all tanphetamine- induced behaviors or whether sase behaviors were more specifically blocked than others. Amphetamine-induced behaviors in the rat are considered to involve two successive phases : hypermotility, including forward movement and rearing; and stereotypy, including sniffing, gnawing, groaning and headweaving (Schiorring, 1971; Segal, 1975). Both subcan- ponents of hypermotility follow the same dose-response curve (Popper, in preparation). With time, activity decreases and stereotypy emerges. The various components of stereotypy are potentiated or blocked by similar agents (Creese and Iversen, 1974; Randrup, 1965). This study was designed to further explore the effect of naloxone on the hypermotility and stereotypy induced by amphetamine in the rat. Methods The subjects were Sprague-Dawley rats weighing 180-250 g. Twenty-four animals were employed in the first experiment and 16 in a replication study. They were housed in groups of 5 with food and water ad libitmn. -- 425