The effects of yohimbine and four other antagonists on amitraz-induced depression of shuttle avoidance responses in dogs

Abstract

The ability of five antagonists to prevent the central nervous system's depressant effects of amitraz in dogs was evaluated using a shuttle avoidance paradigm. All drugs were injected iv into six male dogs trained to avoid a 1-mA shock by jumping over a hurdle within 10 sec of the start of a tone. Dogs were given an antagonist or saline followed in 5 min by 3 mg/kg amitraz dissolved in dimethyl sulfoxide (DMSO) or DMSO alone. After pretreatment with saline, amitraz decreased significantly the x number of avoidance responses and increased significantly the x latencies of avoidance responses. After pretreatment with the α 2-adrenoreceptor antagonist yohimbine (0.1 mg/kg), amitraz no longer decreased the x number of avoidance responses or lengthened the x latencies of avoidance responses. The nonselective α-adrenoreceptor antagonist tolazoline (3.3 mg/kg) prevented amitraz-induced increases in x latencies, but did not prevent the decreases in the x number of avoidances. The α 1-adrenoreceptor antagonist prazosin (1 mg/kg), the muscarinic receptor antagonist atropine (0.04 mg/kg), and the opioid receptor antagonist naloxone (1 mg/kg) did not prevent either of amitraz's effects. The data suggest that the amitraz-induced suppression of avoidance responding is mediated by α 2-adrenoreceptors rather than by α 1-adrenergic, muscarinic, or opioid receptors.