Pharmacology Biochemistry & Behavior, Vol. 15, pp. 513-514, 1981, Printed in the U.S.A. Naloxone Potentiates Shock-Induced Aggressive Behavior in Mice STEFANO PUGLISI-ALLEGRA AND ALBERTO OLIVERIO lstituto di Psicobioiogia e Psicofarmacologia, via Reno, 1 - 00198 Roma, Italy and Istituto di Fisiologia Generale, Universit~ di Roma Received 19 February 1981 PUGLISI-ALLEGRA, S. AND A. OLIVERIO. Naloxone potentiates shock-induced aggressive behavior in mice. PHARMAC. BIOCHEM. BEHAV. 15(3) 513-514, 1981.--Naloxone (0.025 to 0.05 mg/kg IP) potentiates shock-induced aggressive behavior in C57BL/6 mice but not in DBA/2 mice which do not fight in absence of drug, This effect is not related to pain sensitivity since the doses used in this experiment do not lower tail-flick threshold in C57BL/6 mice. These f'mdings are discussed in terms of the role of the endorphin system and of catecholamine related sensory attention in a number of social interactions in the mouse. Naloxone Shock-induced aggressive behavior Endorphins Inbred mice ENDOGENOUS opioids (enkephalins and endorphins) are involved in a number of behavioral patterns and social activ- ities connected to emotionality. Animals treated with nalox- one, a drug which antagonizes the effects of endorphins, are characterized by increased locomotor activity, different signs of social discomfort and enhanced sexual behavior (for review see Panksepp et al. [5]). These behavioral patterns were described in different species ranging from birds to rodents and the functions of the endogenous analgesic systems have been interpreted in terms of adaptive species-specific mechanisms. Differences in the function of the endorphin system and in the behavioral effects of opiates have been described and interpreted in terms of different types of receptors and of their cerebral distribution [9]. In particular morphine or other opiates exert a stimulating effect on the activity of some strains of mice such as C57BL/6 (C57), while they depress or induce freez- ing responses in other strains such as DBA/2 (DBA); these differences have been explained in terms of endogenous opiate receptors and of dopaminergic and noradrenergic re- sponses [2]. C57 and DBA mice are also characterized by different levels of aggressive behavior in a number of tests in response to pharmacological and environmental manipula- tions [6,10]. In the present study these strains of mice were injected with naloxone in order to assess whether or not an inhibition of endogenous opiates results in an increased shock-induced aggressive behavior. METHOD Male C57BL/6 (C57) and DBA/2 (DBA) mice (Charles River, Como, Italy), 11-12 weeks old were used. Shock- induced aggressive behavior was measured in an apparatus in which the bites between two mice are recorded through a counter [7]. The apparatus consists of an experimental chamber (9x9x14 cm). Two holes (1 cm diameter at 1 cm above the grid floor) allow the tails to extend out of the chamber on two opposite walls. A threaded bush previously glued on each tail by means of Bostik is fixed by a nut in the center of a ball bearing, so that the mouse can move freely with no danger to the tail. The two ball bearings work as slip rings for a contact detector. A low current (2 t~A) passing through both mice during biting is amplified by the contact detector so that all bites, but no other body contact, can be recorded by a digital counter. Aggressive behavior was in- duced by shocking simultaneously both mice. The electric shock (0.25 mA) was applied by means of two electrodes to the part of the tail available between the hole and the ball bearing. In our experiments each treatment group consisted of ten pairs of mice per strain. Each session lasted for four minutes in which shocks of 0.5 sec duration were delivered every 3 sec. Prior to each encounter the mice were placed in oppo- site halves of the experimental cage, separated by a sliding door. After a 60 sec adaptation period the sliding door was raised, and shocks were delivered. The experimental cage was cleaned between sessions in order to remove odors. Mice of each pair came from different breeding groups. To study pain sensitivity the tail-flick method was used. Naloxone hydrochloride was injected intraperitoneally 10 minutes before testing at different doses. Control mice were injected with saline. Data were analyzed statistically by single-factor analysis of variance (ANOVA; independent). Further analysis for individual between-group comparisons was carried out by employing the error term of the overall analysis of variance. RESULTS Saline-injected C57 mice are characterized by very low levels of aggressive responses: Figure I shows that naloxone Copyright © 1981 ANKHO International Inc .--0091-3057/81/090513-02500. 70/0