The effect of ipsapirone and S(-)-pindolol on dopamine
release in rat striatum and nucleus accumbens
by
Ichikawa J, Meltzer HY
Department of Psychiatry,
Psychopharmacology Division,
Vanderbilt University School of Medicine,
Nashville, USA.
ichikaj@ctrvax.vanderbilt.edu
Brain Res 1999 Sep 25; 842(2):445-51
ABSTRACTSerotonin (5-hydroxytryptamine, 5-HT)(1A) receptor agonism and 5-HT(2A) receptor antagonism are components in the action of some of the recently developed antipsychotic drugs, e.g., clozapine and ziprasidone. However, studies of the role of 5-HT(1A) receptor agonism in the ability of these drugs to modulate dopamine (DA) release in the nucleus accumbens (NAC), which may be relevant to antipsychotic action, are lacking. Thus, we examined the effect of clinically available agents, ipsapirone, a 5-HT(1A) receptor partial agonist, and the mixed 5-HT(1A/1B)/beta receptor antagonist S(-)-pindolol, on DA release in the NAC compared to the striatum (STR). Ipsapirone produced a biphasic effect; low dose (0.1 mg/kg) decreased, high dose (3 mg/kg) increased and intermediate doses (0.1 and 1 mg/kg) did not change DA release in the NAC, respectively. However, ipsapirone, at all doses (0.3, 1, 3, but not 0.1 mg/kg) increased striatal DA release. S(-)-pindolol (3, 10, but not 1 mg/kg) produced a comparable increase in DA release in the NAC and STR. These results suggest that the ability of lower dose of ipsapirone to decrease DA release in the NAC is more likely to be due to 5-HT(1A) receptor agonism. On the other hand, the effect of higher dose of ipsapirone on striatal DA release may be due to 5-HT(1A) receptor antagonism, as is the case with S(-)-pindolol. The mechanism and clinical significance of these results for developing antipsychotic drugs is discussed.5-HT1a
F11440
Pindolol
Gepirone
Dopamine
Buspirone
Flesinoxan
Ipsapirone
Pindolol (Visken)
Pindolol + buspirone
Ipsapirone v lorazepam
The nucleus accumbens
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