Effect of destruction of central noradrenergic and serotonergic nerve terminals by systemic neurotoxins on the long-term effects of antidepressants on?-adrenoceptors and 5-HT2 binding sites in the rat cerebral cortex

Abstract

Summary The dependence of intact noradrenergic and serotonergic nerve terminals for the decrease in the number ofβ-adrenoceptors and 5-HT₂ binding sites in the cerebral cortex produced by long-term treatment of rats with antidepressant drugs was examined. Noradrenergic nerve terminals were destroyed with the selective noradrenaline neurotoxin DSP4, and serotonergic nerve terminals were destroyed with p-chloroamphetamine (PCA). It was found that lesioning of the noradrenergic nerve terminals abolished the decrease inβ-adrenoceptors produced by desipramine, mianserin and zimeldine and partially antagonized that of theβ-adrenoceptor agonist clenbuterol. PCA pretreatment did not antagonize the long-term effects on theβ-adrenoceptor produced by these compounds. Lesioning of serotonergic nerve terminals affected the down-regulation of 5-HT₂ binding sites produced by long-term treatment with mianserin, desipramine and amiflamine. DSP4 pretreatment partially abolished the down-regulation of 5-HT₂ binding sites produced by long-term treatment with desipramine, while the effects of mianserin and amiflamine were unaffected by pretreatment with DSP4.