Effects of pretreatment with 6-hydroxydopamine or noradrenergic receptor blockers on the clonidine-induced distruption of conditioned avoidance responding.

The effects of clonidine were assessed on conditioned avoidance responses (CAR) in control, 6-hydroxy-dopamine (6-OHDA)- and vehicle-treated rats, using a shuttle box device. Clonidine (100--400 micrograms/kg) produced a significant decrease of CAR in control and vehicle-treated animals. On the other hand, avoidance responding was only slightly inhibited in the 6-OHDA-lesioned rats. Pretreatment with the alpha-adrenergic blocking drugs yohimbine or phentolamine (1--8 mg/kg) prevented the CAR disrupting effects of clonidine. When animals were pretreated with the beta-adrenergic blocking agent propranolol (1--8 mg/kg) the ensuing injection of clonidine caused a greater CAR depression. Our results further support the hypothesis relating the conditioned performance depression observed after clonidine to the activation of a presynaptic negative feedback mechanism mediated by alpha-adrenoceptors. It is also suggested that propranolol increases the clonidine inhibition through the blockade of a positive feedback mechanism dependent on the activation of presynaptic beta-receptors.