Yawning and suppression of exploration in amphetamine-treated rats, incompatibility with the autoreceptor hypothesis

The hypothesis that yawning and suppression of exploration, induced by low doses of dopamine agonists, are mediated by stimulation of dopamine autoreceptors was tested by studying the influence of amphetamine on these behavioural models and on extracellular levels of dopamine sampled by microdialysis. Behaviour was measured in a holeboard apparatus. A low dose of amphetamine (0.2 mg/kg) caused slight activation of habituated rats. The same dose of amphetamine completely counteracted the decrease in extracellular dopamine levels caused by pergolide (0.02 mg/kg) and, instead, elevated the dopamine levels to 300% above baseline. The same or higher doses of amphetamine (0.5-1.0 mg/kg) did not completely antagonise suppression of exploration or yawning induced by apomorphine (0.05 mg/kg) or pergolide (0.02 mg/kg). The results suggest that both yawning and suppression of exploration induced by low doses of dopamine agonists are not mediated by dopamine autoreceptors, since these behaviours could be elicited when the extracellular levels of dopamine were elevated above baseline. The alternative hypothesis that these behaviours are mediated by sensitive post-synaptic receptors is suggested. It was also found that combined treatment with SCH 23390 (0.05 mg/kg) and amphetamine (2 mg/kg) induced yawning, which further supports the new hypothesis.