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Selective serotonin
reuptake inhibitors reduce the spontaneous activity of dopaminergic
neurons in the ventral tegmental area.
Di Mascio M,
Di Giovanni G, Di Matteo V, Prisco S, Esposito E.
Istituto di
Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa
Maria Imbaro (Chieti), Italy.
Electrophysiological techniques
were used to study the effects of paroxetine, sertraline, and
fluvoxamine on the basal activity of dopaminergic neurons in the ventral
tegmental area (VTA) of rats. Acute i.v. administrations of paroxetine
(20-1280 microg/kg), sertraline (20-1280 microg/kg), and fluvoxamine
(20-1280 microg/ kg) caused a slight but significant reduction in the
firing rate of the VTA dopaminergic cells studied. Paroxetine produced a
maximal inhibitory effect of 10 +/- 11% at the cumulative dose of 160
microg/kg. Sertraline induced a dose-related inhibition of VTA
dopaminergic neurons, which reached its maximum (10 +/- 7%) at the
cumulative dose of 1280 microg/kg. The effect of fluvoxamine on the
basal firing rate of VTA dopaminergic neurons was more pronounced as
compared to that of paroxetine and sertraline, in that it produced a
maximal inhibition of 17 +/- 12% at the cumulative dose of 1280
microg/kg. Acute i.v. injections of paroxetine (20-1280 microg/kg),
sertraline (20-1280 microg/kg), and fluvoxamine (20-5120 microg/kg)
caused a dose-dependent decrease in the basal firing rate of
serotonergic neurons in the dorsal raphe nucleus (DRN). Paroxetine and
sertraline stopped the spontaneous firing of serotonergic neurons at the
cumulative dose of 1280 microg/kg, whereas fluvoxamine reached the same
effect only at the cumulative dose of 5120 microg/kg. Pretreatment with
the 5-HTA1A receptor antagonist tertatolol (1 mg/kg, i.v.) reduced the
inhibitory effects of paroxetine, fluvoxamine, and sertraline on the
basal activity of serotonergic neurons in the DRN. Administration of
tertatolol induced a 15-fold increase in the ED50 for fluvoxamine. The
antagonistic effect of tertatolol was much less evident in blocking the
inhibitory action exerted by paroxetine and sertraline on the activity
of serotonergic neurons. Pretreatment with tertatolol (1 mg/kg, i.v.)
potentiated the inhibitory effect of fluvoxamine on the basal activity
of VTA dopaminergic neurons. Tertatolol did not affect the inhibitory
action exerted by paroxetine and sertraline on these neurons. It is
concluded that inhibition of the basal firing rate of dopaminergic
neurons in the VTA is a common characteristic of selective serotonin
reuptake inhibitors (SSRIs). The effects of SSRIs on VTA dopaminergic
cell activity might be relevant for their therapeutic action and may
explain the origin of the reported cases of akathisia.
PMID:
9744293 [PubMed - indexed for MEDLINE]
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