Serotonergic modulation of extrapyramidal motor disorders in mice and rats: Role of striatal 5-HT3 and 5-HT6 receptors

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

“…8,29) In our studies, neither antagonist for 5-HT 4 (GR-125487), 5-HT 5a (SB-699551), nor 5-HT 7 (SB-269970) receptors affected against induction of antipsychotic-induced EPS. 29) 3.…”

“…8,29) In our studies, neither antagonist for 5-HT 4 (GR-125487), 5-HT 5a (SB-699551), nor 5-HT 7 (SB-269970) receptors affected against induction of antipsychotic-induced EPS. 29) 3. CONCLUSION AND PERSPECTIVE Extrapyramidal motor disorders are the core symptom of Parkinson's disease and the most frequently observed side effects of antipsychotics in the treatment of schizophrenia and related psychotic diseases.…”

“…31,32) In our studies, activation of the serotonergic system by 5-hydroxytryptophan (5-HTP) significantly potentiated haloperidol-induced catalepsy and this 5-HTPpotentiated EPS was also suppressed by systemic treatments or intrastriatal microinjections of ondansetron. 29) These findings indicate that postsynaptic 5-HT 3 receptors in the striatum are involved in the induction or potentiation of extrapyramidal disorders and blockade of the striatal 5-HT 3 receptors can alleviate antipsychotic-induced EPS (Fig. 2 and Table 1).…”

“…4) Although an early study reported that the 5-HT 6 antagonist Ro 04-6790 failed to affect haloperidol-induced catalepsy, 33) we recently demonstrated that the 5-HT 6 antagonist SB-258585 alleviated haloperidol-induced bradykinesia and catalepsy. 29,30) In addition, the EPS-potentiating action of 5-HTP was also blocked by systemic injection of SB-258585 or its microinjection into the striatum, implying that blockade of the striatal 5-HT 6 receptors is at least in part involved in alleviating antipsychotic-induced EPS (Fig. 2 and Table 1).…”

“…[28][29][30] Recent clinical studies also showed that ondansetron significantly reduced the incidence and severity of antipsychotic-induced EPS (e.g., akathisia and parkinsonism) in patients with chronic schizophrenia. 31,32) In our studies, activation of the serotonergic system by 5-hydroxytryptophan (5-HTP) significantly potentiated haloperidol-induced catalepsy and this 5-HTPpotentiated EPS was also suppressed by systemic treatments or intrastriatal microinjections of ondansetron.…”