Clonidine Inhibition Research Articles

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

The effects of clonidine assessed on conditioned avoidance responses (CAR) in control, 6-hydroxydopamine (6-OHDA)- and vehicle-treated rats, using a shuttle box device. Clonidine (100–400 μg/kg) produced a significant decrease of CAR in control and vehicle-treated animals. On the other hand, avoidance responding was onyl slightly inhibited in the 6-OHDA-lesioned rats. Pretreatment with the α-adrenergic blocking drugs yohimbine or phentolamine (1–8 mg/kg) prevented the CAR disrupting effects of clonidine. When animals were pretreated with the β-adrenergic blocking agent propanolol (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 α-adrenoceptors. It is also suggested that propanolol increases the clonidine inhibition through the blockade of a positive feedback mechanism dependent on the activation of presynaptic β-receptors.

α-Adrenergic modulation of hypothalamic self-stimulation: Effects of phenoxybenzamine, yohimbine, dexamphetamine and their interactions with clonidine

The α-adrenoceptor agonist clonidine (12.5–50.0 μg/kg) produced a dose dependent increase in the latency to initiate lateral hypothalamic stimulation. The insurmountable postsynaptic α-adrenoceptor antagonist phenoxybenzamine (0.2–0.8 mg/kg) had no effect on self-stimulation by itself, but potentiated the inbibitory effects of clonidine. The fact that the concurrent escape behavior to thr intracranial stimulation was unchanged by either clonidine or the phenoxybenzamine-clonidine combination suggests that the inhibition is specific to the rewarding component of hypothalamic stimulation. Yohimbine (0.5–2.0 mg/kg) produced a dose-dependent increase in both response latencies. This lack of behavioral specificity may reflect yohimbine's wide range of pharmacological activity. Dexamphetamine (0.25–0.50 mg/kg) reversed clonidine's inhibition of self-stimulation reward in a specific and dose-dependent fashion. This reversal could be blocked by previous inhibition of catecholamine synthesis with α-methyl-p-tyrosine. These data support the concept that the α-adrenoceptors play a critical role in the modulation of hypothalamic self-stimulation reward. They further suggest that the inhibitory effects of clonidinen self-stimulation reward represent an agonist effect on presynaptic α-adrenoceptors.