Effect of destruction of central noradrenergic and serotonergic nerve terminals by systemic neurotoxins on the long-term effects of antidepressants on beta-adrenoceptors and 5-HT2 binding sites in the rat cerebral cortex.
The dependence of intact noradrenergic and serotonergic nerve terminals for the decrease in the number of beta-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 in beta-adrenoceptors produced by desipramine, mianserin and zimeldine and partially antagonized that of the beta-adrenoceptor agonist clenbuterol. PCA pretreatment did not antagonize the long-term effects on the beta-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.
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002976:Clenbuterol / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000378:metabolism; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D015031:Zimeldine / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology
D000588:Amines; D000928:Antidepressive Agents; D001596:Benzylamines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D008803:Mianserin; D012701:Serotonin; D015031:Zimeldine; D013134:Spiperone; D004082:Dihydroalprenolol; D010133:p-Chloroamphetamine; C025293:alaproclate; D000409:Alanine; C012102:DSP 4; D003891:Desipramine; D002976:Clenbuterol