Regulation of Cholinergic Activity in the Rat Hippocampus: In Vivo Effects of Oxotremorine and Fenfluramine

Abstract

Oxotremorine (OTMN) is a powerful muscarinic receptor agonist whose profound effects on cholinergic neurons of the hippocampus have been particularly well characterized. The drug increases the content and decreases the turnover (TR_ACh) and release of acetylcholine (ACh). In addition, it depresses the sodium dependent high affinity uptake of choline (SDHACU) into the cholinergic terminals (see Table 1). The biochemical effects are indicative of a depressant action of OTMN dn cholinergic neurons. It is implicit that when the muscarinic receptor sites are occupied by this agonist the regulatory mechanism of ACh synthesis receives a signal to slow down its activity. The location of the sites at which the signal starts is a matter of controversy at the moment. OTMN acts directly on muscarinic receptors which may be located either on the presynaptic cholinergic terminals as suggested by Szerb et al. (23) or postsynaptically on non-cholinergic neurons, and thereby operates through a neuronal feedback loop. The latter hypothesis appears more likely since it has been found that reserpine, as well as atropine blocked the effect of OTMN on whole brain (3) and striatal (24) ACh content.