Title :

Early Life Stress Causes Refractoriness to Haloperidol-Induced Catalepsy

Author(s) :

Marrocco, Jordan [Auteur]
Mairesse, Jérôme [Auteur]
Bucci, Domenico [Auteur]
Lionetto, Luana [Auteur]
Battaglia, Giuseppe [Auteur]
Consolazione, Michol [Auteur]
Ravasi, Laura [Auteur]
Simmaco, Maurizio [Auteur]
Morley-Fletcher, Sara [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Maccari, Stefania [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Nicoletti, Ferdinando [Auteur]

Journal title :

Molecular pharmacology

Volume number :

84

Pages :

244-251

Publication date :

2013-08-01

ISSN :

1521-0111

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Glycostress

Submission date :

2020-02-12T15:12:21Z
2021-03-18T13:42:01Z