Posted by Amelia_in_StPaul on April 20, 2009, at 17:03:12
In reply to Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark, posted by sowhysosad on April 5, 2009, at 16:39:40
Not all of the SSRIs do the same thing. Fluoxetine has a different effect on dopamine than other SSRIs.
Fluoxetine as monotherapy in psychotic depression:
Report of 4 cases(Excerpt) Recent studies demonstrate that serotonin exhibits a regulatory dopaminergic action by inhibiting the release of dopamine through 5-HT2A somatodendritic receptors in the surface of dopaminergic neurons; thus 5-HT2A antagonists (Altanserin) and 5-HT1A agonists (which may exert subtle inhibitory effects on dopaminergic cell bodies in the substantia nigra by means of autoreceptors ; Kelland, M.D. et al., 1990) or injury to the serotonergic tracts (Dray, A. et al., 1978), produce a disinhibition of dopaminergic neurons in the middle brain with modest increases in the release (Ennis, C. et al.,1981) and possibly in the synthesis of dopamine (Spampinato, U. et al., 1985) in the nucleus accumbens and the prefrontal cortex (Waldmeier, P.C. & Delini-Stula, A.A., 1979; Nedergaard, S. et al., 1988; Kelland, M.D. et al., 1990; Leysen, J.E. et al., 1994). On the other hand, some of the effects of the serotonin in the dopaminergic system can be mediated in indirect form through the modulation of the GABA and the cholinergic system (Dewey, S.L. et al., 1993). Fluoxetine and its active metabolite, norfluoxetine, have a serotonergic profile inhibiting serotonin reuptake the synaptic cleft (Lucas, R.A., 1992). However, the effect of the fluoxetine on other monoaminergic systems is not clearly established. Fluoxetine has been associated with the development of bradykinesia and rigidity, akathisia, shuffling gait, cogwheeling, tremor and akathisia, possibly by the activation of 5-HT2a receptors in dopaminergic neurons (Bouchard, R.H. et al., 1989; Lipinski, J.F. Jr. et al., 1989; Arya, D.K., 1994; Coulter, D.M. & Pillans, P.I., 1995) in a proportion similar to 1 out of 1000 individuals that consume SSRIs (Choo, V ., 1993). Fluoxetine, by increasing the serotonergic activity in the projections toward the substantia nigra from the dorsal raphe nuclei, can inhibit the firing rate of dopaminergic neurons, in such a way that the dopamine blockers in combination with fluoxetine can lead to extrapyramidal effects in patients even when they havent experienced adverse effects when treated only with antipsychotics (Levinson, M.L. et al., 1991). In spite of such findings, fluoxetine has relatively few side effects, especially when compared with the tricyclic antidepressants (Cooper, G.L., 1988) or with Amoxapine (Anton, R.F. & Burch, E.A., 1990).
Effects of fluoxetine on dopamine D2 receptors in the human brain: a positron emission tomography study
We have previously reported that repeated dosing with the selective serotonin reuptake inhibitor (SSRI) citalopram decreases striatal [11C]raclopride binding in healthy volunteers. As the SSRI-class antidepressant drugs are believed to have a similar mechanism of action, we wanted to explore whether the prototype SSRI drug, fluoxetine, shares the effects of citalopram on subcortical dopamine neurotransmission. Eight healthy male volunteers were studied using a randomized double-blind placebo-controlled study design. Striatal and thalamic D2-receptor binding was measured at baseline, after a single oral dose (20 mg) of fluoxetine, and after repeated dosing (2 wk, 20 mg/d). The D2-receptor binding potential (BP) was assessed using [11C]raclopride and 3D positron emission tomography. Repeated dosing of fluoxetine decreased BP in the right medial thalamus (p=0.022). Fluoxetine did not decrease striatal BP, but there was a trend (p=0.090) towards increased BP in the left putamen after repeated dosing. A single dose of fluoxetine did not affect BP in the thalamus or striatum. Fluoxetine appears to have a regionally selective effect on the dopaminergic neurotransmission in various areas of the brain. The current results after fluoxetine together with our previous data on citalopram suggest that the modulatory effects of these drugs on striatal dopaminergic neurotransmission are different upon repeated dosing and further substantiates pharmacological differences between SSRI-class drugs.
poster:Amelia_in_StPaul
thread:883495
URL: http://www.dr-bob.org/babble/neuro/20090129/msgs/891800.html