Clavulanic acid induces penile erection and yawning in male rats: comparison with apomorphine

The beta-lactamase inhibitor clavulanic acid induced penile erection and yawning in a dose dependent manner when given intraperitoneally (IP, 0.05–5 mg/kg), perorally (OS, 0.1–5 mg/kg) and intracereboventricularly (ICV, 0.01–5 μg/rat) to male rats. The effect resembles that of the dopamine receptor agonist apomorphine given subcutaneously (SC) (0.02–0.25 mg/kg), although the responses of the latter followed a U inverted dose–response curve, disappearing at doses higher than 0.1 mg/kg. Clavulanic acid responses were reduced by about 55% by haloperidol, a dopamine D2 receptor antagonist (0.1 mg/kg IP), and by d(CH2)5Tyr(Me)2-Orn8-vasotocin, an oxytocin receptor antagonist (2 μg/rat ICV), both given 15 min before clavulanic acid. A higher reduction of clavulanic acid responses (more than 80%) was also found with morphine, an opioid receptor agonist (5 mg/kg IP), and with mianserin, a serotonin 5HT2c receptor antagonist (0.2 mg/kg SC). In contrast, no reduction was found with naloxone, an opioid receptor antagonist (1 mg/kg IP). The ability of haloperidol, d(CH2)5Tyr(Me)2-Orn8-vasotocin and morphine to reduce clavulanic acid induced penile erection and yawning suggests that clavulanic acid induces these responses, at least in part, by increasing central dopaminergic neurotransmission. Dopamine in turn activates oxytocinergic neurotransmission and centrally released oxytocin induces penile erection and yawning. However, since both penile erection and yawning episodes were reduced not only by the blockade of central dopamine and oxytocin receptors and by the stimulation of opioid receptors, which inhibits oxytocinergic neurotransmission, but also by mianserin, an increase of central serotonin neurotransmission is also likely to participate in these clavulanic acid responses.