Naltrexone blocks amphetamine-induced hyperactivity, but not disruption of social and agonistic behavior in mice and squirrel monkeys.

Significant anatomical overlap of opioid and dopamine receptors as well as reciprocity of control over synthesis, metabolism, and release of opioid peptides and dopamine in brain suggests functional interactions between the two systems. In the first of two studies, the behavioral effects of amphetamine and naltrexone alone, and in combination were studied in established groups of socially interacting squirrel monkeys. Naltrexone (0.1-10.0 mg/kg, IM) increased locomotion and marking behavior in subordinate monkeys. The frequency of social initiatives directed at treated subordinate monkeys by untreated members of the group was also increased. The behavior of dominant monkeys was relatively unaffected, except at the highest dose when autonomic distress was also evident. The frequency of walking bouts by both dominant and subordinate monkeys was increased by amphetamine (0.1-0.6 mg/kg, IM), and the social behavior of dominant monkeys was disrupted by drug treatment. Naltrexone (0.1 mg/kg, IM) significantly antagonized amphetamine's effects on motor behavior, and enhanced or did not affect amphetamine's effects on social behavior. In a second study, the interaction of amphetamine (0.63-10.0 mg/kg, IP) and naltrexone (0.1-10.0 mg/kg, IP) on the behavior of resident male mice during confrontations with a male intruder was studied. Naltrexone selectively reduced the frequency of attack at the highest dose tested. Amphetamine increased locomotor activity and decreased attack and threat behavior in resident mice. A low dose of naltrexone (1.0 mg/kg, IP) blocked amphetamine's effects on locomotion and enhanced the disruption of aggressive behavior. The amphetamine-naltrexone interaction on locomotor activity in mice and monkeys is consistent with opioid receptor modulation of dopamine mediated functions.(ABSTRACT TRUNCATED AT 250 WORDS)