Presynaptic alpha-adenoceptors: the depression of self-stimulation by clonidine and its restoration by piperoxane but not by phentolamine or phenoxybenzamine.
Depression of self-stimulation by clonidine has been ascribed to continuous direct stimulation of alpha-adrenoceptors with consequent disruption of reinforcement signals thought to be conveyed by noradrenergic pathways. This suggestion was tested by administration of alpha-receptor blocking agents (piperoxane, phentolamine and phenoxybenzamine, PBZ) differing in their affinity for pre- and post-synaptic receptor sites. Piperoxane in low doses (0.55-5.0 mg/kg) previously reported to cause specific blockade of pre-synaptic receptors implicated in negative feedback circuits, caused a significant increase in self-stimulation rate and strongly antagonized the depression of self-stimulation by clonidine (0.15 mg/kg). A larger dose of piperoxane (45 mg/kg) and graded doses of phentolamine and PBZ, affecting both pre- and post-synaptic receptors, depressed self-stimulation, and did not antagonize clonidine-induced depression of self-stimulation. It is concluded that depression of self-stimulation by clonidine may depend on clonidine-induced inhibition of NA release exerted via presynaptic receptors, and that the effect of clonidine is not necessarily evidence that noncontingent adrenergic stimulation disrupts reinforcement.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D010883:Piperoxan / Q000494:pharmacology*; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012653:Self Stimulation / Q000187:drug effects*; D013238:Stereotaxic Techniques; D013569:Synapses / Q000187:drug effects*
D010880:Piperidines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010883:Piperoxan; D003000:Clonidine; D010646:Phentolamine