Serotonin Agonists Reduce Dopamine Synthesis in the Striatum Only when the Impulse Flow of Nigro‐Striatal Neurons Is Intact

Abstract

The effects of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) and m-chlorophenylpiperazine (CPP), two 5-hydroxytryptamine (5-HT, serotonin) agonists, on the accumulation of 3,4-dihydroxyphenylalanine (DOPA] were studied in the striatum of rats treated with gamma-butyrolactone (GBL). Unlike 2 mg/kg i.p. apomorphine, neither 5 mg/kg i.p. 5-MeO-DMT nor 2.5 mg/kg i.p. CPP significantly reduced the GBL-induced increase in DOPA accumulation in the striatum. 5-MeO-DMT and CPP significantly reduced DOPA accumulation in animals that had received the aromatic amino acid decarboxylase inhibitor Ro 4-4602 but not GBL. 5-HT (10 micrograms in 0.5 microliter) injected in the substantia nigra, pars compacta, like GBL, significantly increased Ro 4-4602-induced accumulation of DOPA in the striatum. The data indicate that 5-HT agonists can reduce 3,4-dihydroxyphenylethylamine (DA, dopamine) synthesis in the striatum of rats only when the impulse flow of DA neurons is intact. An indirect effect through mechanisms controlling DA synthesis in the striatum, for instance cholinergic and GABA-ergic neurons, is suggested.

Characterization of the effects of serotonin on the release of [3H]dopamine from rat nucleus accumbens and striatal slices

“…However, in neither of these studies was it demonstrated that the effect of serotonin on basal overflow of 3H was completely blocked. The results of the present study are in agreement with evidence that serotonin receptors do not modulate DA synthesis in the striatum (29,31) and that the effect of serotonin is post-synaptic to dopaminergic neurons in the nucleus accumbens (13,16) and striatum (14,15).…”

Serotonergic modulation of the discriminative-stimulus effects of cocaine in squirrel monkeys

“…Although the discriminative effects of cocaine have been linked primarily to dopamine (McKenna and Ho 1980;Woolverton 1991;Spealman et al 1992), it is possible that 5-HT plays a direct, but less significant role, and that antagonism of serotonin attenuated the cocaine discriminative stimulus. Serotonergic modulation of DA has been observed (Nicolaou et al 1979;Spampinato et al 1985;De Simoni et al 1987), but it appears that 5-HT may inhibit dopaminergic activity (Fibiger and Miller 1977;Dray et al 1978;Klelland 1990), and 5-HT was positively related to the discriminative effects of cocaine in the present study.…”

Serotonergic modulation of striatal D2 dopamine receptor binding in humans measured with positron emission tomography

“…Several animal studies have suggested that serotonin agonists and re-uptake inhibitors increase striatal dopamine synthesis or release in animals (Benloucif and Galloway 1991;Huang and Nichols 1993), but other studies have given opposite results (Awazi and Guldberg 1978;Spampinato et al 1985;Baldessarini and March 1990). A recent study which used both PET and microdialysis methods showed that 5-HT2 antagonists markedly increased extracellular dopamine concentration in striatum, whereas 5-HT re-uptake inhibitor citalopram decreased the dopamine concentration (Dewey et al 1995).…”

“…On the basis of electrophysiological, microdialysis and positron emission tomography (PET) studies in animals, it has been suggested that the psychotropic effects of serotonergic drugs may be mediated through the serotonergic modulation of the striatal dopamine activity, although the findings have remained controversial (Awazi and Guldberg 1978;Waldmeier and Delini-Stula 1979;Spampinato et al 1985;Sinton and Fallon 1988;Sorenson et al 1989;Baldessarini and Marsh 1990;Benloucifand Galloway 1991;Huang and Nichols 1993;Dewey et al 1995). However, in most of these studies, the effects of the serotonergic manipulation on the dopamine activity were measured in animals during anaesthesia.…”