Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis

5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

“…Since psilocybin also acts upon 5-HT 1A receptors (Buckholtz et al 1990;McKenna et al 1990) and stimulation of 5-HT 1A autoreceptors is expected to enhance the dopaminergic tone (Neal-Beeliveau et al 1993), one might speculate that psilocybin increases striatal dopamine release through a concomitant stimulation of both 5-HT 1A and 5-HT 2A receptors. This hypothesis is supported by the finding that 5-HT 1A agonists can facilitate dopamine release in the striatum and nucleus accumbens (Benloucif and Galloway 1991), while 5-HT 1A antagonist have been reported to inhibit dopamine release in these brain regions (Parson and Justice 1993;Boulenguez et al 1996;Nomikos et al 1996). Furthermore, recent studies in rats demonstrated that the changes in locomotor activity produced by the 5-HT 1A agonist 8-OH-DPAT (Hillegaart et al 1995) or the classic indolehallucinogen LSD were attenuated by pretreatment with the selective 5-HT 1A antagonist WAY-100,635 (Sipes and Geyer 1995;Krebs-Thomson and Geyer 1996).…”

“…This mechanism is consistent with recent studies demonstrating increased striatal dopamine levels after acute administration of the 5-HT releaser and uptake inhibitor fenfluramine (Smith et al 1997) and chronic administration of the 5-HT uptake inhibitor citalopram (Tiihonen et al 1996) in normal subjects as assessed by PET and [ 11 C]raclopride. In animal studies, local application of 5-HT or 5-HT agonists by means of microdialysis was also reported to increase extracellular DA in the striatum (Benloucif and Galloway 1991;Benloucif et al 1993;Bonhomme et al 1995) and nucleus accumbens (Guan and McBride 1989;Parson and Justice 1993;Boulenguez et al 1996). However, there is a minority of studies reporting an inhibitory influence of serotonergic stimulation on striatal dopamine concentration (Dewey et al 1995;Kapur and Remington 1996).…”

“…For example, there is evidence that serotonin may inhibit (de Belleroche and Bradford 1980;Ennis et al 1981;Westfall and Tittermary 1982;Blandina et al 1988) as well as stimulate DA release in the striatum (Benloucif et al 1993;West and Galloway 1996;De Deurwaerdere et al 1997). Similarly, local application of 5-HT or 5-HT agonists have been shown to reduce (de Belleroche and Gardiner 1982) and facilitate dopamine efflux in the nucleus accumbens (Guan and McBride 1989;Parson and Justice 1993). In respect to the 5-HT 2 receptor agonist properties of psilocybin, it is of particular note that 3,4-methylenedioxymethamphetamine (MDMA), a potent 5-HT releasing agent, has been shown to increase impulse-mediated striatal dopamine release through 5-HT 2 receptor activation (Schmidt et al 1992;Palfreyman et al 1993;Schmidt et al 1994;Yamamoto et al 1995;Gudelsky and Nash 1996).…”

Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

“…The presence of the neuronal pool of dopamine within the dorsal raphe and the significant increase of 5-HT and dopamine levels were described in this brain region following the local administration of amphetamine [46]. Parsons and Justice [47] observed that 5-HT increases extracellular dopamine concentrations in the nucleus accumbens. On the other hand, the dopaminergic neurons have 5-HT receptors that permit the tonic control of dopamine release in the midbrain, striatum and nucleus accumbens [48].…”

Involvement of 5‐HT3 receptors in the nucleus accumbens in the potentiation of cocaine‐induced behaviours in the rat

“…Fluoxetine has been shown to increase extracellular 5-HT levels in the NAc (Guan & McBride, 1988), but failed to alter the dopamine levels (Guan & McBride, 1988;Tanda et al, 1994;Sakaue et al, 2000), although 5-HT applied into the NAc increased the extracellular dopamine levels (Parsons & Justice, 1993). This facilitatory e ect of perfused 5-HT on extracellular dopamine levels in the NAc was attenuated by MDL 72222, a 5-HT 3 receptor antagonist (Parsons & Justice, 1993), which is consistent with an increase of dopamine release following 5-HT 3 receptor activation in rat forebrain regions (Jiang et al, 1990;Chen et al, 1991). Hence, stimulation of 5-HT 3 receptors in the NAc, followed by an increased dopamine release may account for¯uoxetine's facilitatory properties on cocaine-induced locomotor and head bobbing activities in rats, which is supported by the antagonism of its facilitatory e ect by ondansetron in the present study.…”