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Early life stress causes refractoriness to haloperidol-induced catalepsy.

Abstract：

:The use of classic antipsychotic drugs is limited by the occurrence of extrapyramidal motor symptoms, which are caused by dopamine (DA) receptor blockade in the neostriatum. We examined the impact of early-life stress on haloperidol-induced catalepsy using the rat model of prenatal restraint stress (PRS). Adult "PRS rats," i.e., the offspring of mothers exposed to restraint stress during pregnancy, were resistant to catalepsy induced by haloperidol (0.5-5 mg/kg i.p.) or raclopride (2 mg/kg s.c.). Resistance to catalepsy in PRS rats did not depend on reductions in blood or striatal levels, as compared with unstressed control rats. PRS rats also showed a greater behavioral response to the DA receptor agonist, apomorphine, suggesting that PRS causes enduring neuroplastic changes in the basal ganglia motor circuit. To examine the activity of this circuit, we performed a stereological counting of c-Fos(+) neurons in the external and internal globus pallidus, subthalamic nucleus, and ventral motor thalamic nuclei. Remarkably, the number of c-Fos(+) neurons in ventral motor thalamic nuclei was higher in PRS rats than in unstressed controls, both under basal conditions and in response to single or repeated injections with haloperidol. Ventral motor thalamic nuclei contain exclusively excitatory projection neurons that convey the basal ganglia motor programming to the cerebral cortex. Hence, an increased activity of ventral motor thalamic nuclei nicely explains the refractoriness of PRS rats to haloperidol-induced catalepsy. Our data raise the interesting possibility that early-life stress is protective against extrapyramidal motor effects of antipsychotic drugs in the adult life.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Marrocco J,Mairesse J,Bucci D,Lionetto L,Battaglia G,Consolazione M,Ravasi L,Simmaco M,Morley-Fletcher S,Maccari S,Nicoletti F

doi

10.1124/mol.113.085530

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

244-51

issue

2

eissn

0026-895X

issn

1521-0111

pii

mol.113.085530

journal_volume

84

pub_type

杂志文章

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