Blockade of intracranial self-stimulation by antipsychotic drugs: failure to correlate with central alpha-noradrenergic blockade.
The involvement of central alpha-noradrenergic receptors in intracranial self-stimulation (ICSS) was studied. Dose-response curves were established for the blockade of ICSS by the antipsychotic drugs chlorpromazine, thioridazine, clozapine, and pimozide and the alpha-antagonist phenoxybenzamine. Antagonism of the facilitation, produced by the central alpha-agonist clonidine, of flexor withdrawal reflexes in the reserpinized spinal rat was used to assess the central alpha-blocking potency of the same drugs, and dose-response curves were established. No correlation was found between central alpha-blockade, as reflected by the ED50 for blockade of clonidine-facilated spinal reflexes, and the ED50 for blockade of ICSS. Pimozide blocked ICSS at doses virtually devoid of central alpha-blocking activity, while phenoxybenzamine was a potent alpha-antagonist and a weak blocker of ICSS. The lack of correlation between central alpha-blockade and decreased ICSS suggests that alpha-receptors are not critically involved in self-stimulation behavior.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003864:Depression, Chemical; D004558:Electric Stimulation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010643:Phenoxybenzamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects; D012653:Self Stimulation / Q000187:drug effects*; D013881:Thioridazine / Q000494:pharmacology; D013997:Time Factors
D014150:Antipsychotic Agents; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010868:Pimozide; D003024:Clozapine; D013881:Thioridazine; D002746:Chlorpromazine