Avoidance learning and mechanism of the protective effect of apomorphine against hypoxia

We have analyzed a conditioned avoidance response (CAR) in rats, under both normoxia and hypobaric hypoxia (300 torr), to try to elucidate the mechanism of apomorphine's protective effect against hypoxia. The resistance to hypoxia is markedly increased by apomorphine (1 mg/kg i.p.) and, to a lesser degree, by an alpha-adrenergic pre-synaptic (yohimbine 1 mg/kg i.p.) or post-synaptic (phenoxybenzamine 1 mg/kg i.p.) blocker. The anti-hypoxic property of apomorphine is not altered when associated with domperidone (0.5 mg/kg i.p.), a peripheral blocker of the dopaminergic receptors. Resistance to hypoxia is decreased by propranolol (1 mg/kg i.p.) and pimozide (1 mg/kg i.p.). It is not modified by tylciprine (2 mg/kg i.p.) or by metergoline (2.5 mg/kg i.p.), a blocker of the 5-hydroxytryptamine (5 H T) receptors. However, the association of any of the above pharmacological agents with apomorphine destroys apomorphine's anti-hypoxic effect. There has even been shown a positive potentialisation ( i.e. an increase of the inhibitory effect) between apomorphine, hypoxia, and the added drug. This potentialisation is already noticeable under normoxia for the association of each of the drugs with apomorphine. Free alpha, beta adrenergic, cerebral dopaminergic, and serotoninergic receptors and an intact amine metabolic pathway therefore seem required for apomorphine to develop its anti-hypoxic activity.