Details

Autor(en) / Beteiligte

• GOLDMAN, MARK EVAN

Titel

EFFECTS OF ANTIDEPRESSANTS ON THE CENTRAL CHOLINERGIC NERVOUS SYSTEM

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

1981

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• The purpose of this investigation was to study the effects of antidepressants on the cholinergic system after acute and chronic drug administration. Drugs were first divided into highly potent, moderately potent or weak anticholinergic categories based upon each compound's ability to displace ('3)H-QNB from synaptosomal membranes. One antidepressant and one non-antidepressant with similar anticholinergic properties were chosen as representative agents of each anticholinergic potency category. High affinity choline uptake was used as an indicator of the turnover rate of acetylcholine. Acute administration of amitriptyline or atropine (highly potent anticholinergics) increased choline uptake levels in the hippocampus and striatum. After 30 days pretreatment with either drug, an acute challenge dose no longer altered choline uptake in either region. Choline uptake levels were also unchanged following an amitriptyline challenge in rats chronically pretreated with atropine. Imipramine and thioridazine (moderately potent anticholinergics) increased choline uptake only in the striatium. After chronic drug treatment followed by a challenge dose, choline uptake levels were not significantly different from controls. After acute administration, the effects of nomifensine and d-amphetamine differed on striatal choline uptake. Following chronic administration neither agent altered choline uptake. Changes in muscarinic receptor distribution were determined after chronic drug administration. Atropine caused an elevation of receptor density in the cortex, hippocampus and striatum. Amitriptyline elevated the muscarinic receptor density only in the cortex. The other agents did not alter muscarinic receptor density in the regions examined. The results of the biochemical studies correlated with several behavioral experiments designed to examine the anticholinergic properties of the antidepressants and changes in muscarinic receptor-mediated processes. The results of these studies show that tolerance can occur to the central cholinergic nervous system effects of antidepressants. Since the central cholinergic actions of antidepressant drugs matched the central actions of anticholinergic drugs lacking clinical antidepressant activity, it was concluded that the effects of antidepressants on the central cholinergic nervous system are more closely related to the side effects of these drugs than to their mechanism of therapeutic action.