Effects of prenatal stress on dopamine D2 receptor asymmetry in rat brain

Adrover, Ezequiela; Berger, María Alejandra; Pérez, Adriana; Tarazi, Frank I.; Antonelli, Marta C.

doi:10.1002/syn.20389

Cited by 24 publications

(14 citation statements)

References 22 publications

(34 reference statements)

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“…As a word of caution, however, the GPe, Gpi, and STN contain interneurons in addition to projection neurons, and the real significance of c-Fos 1 neuronal counting in the overall activity of these nuclei is uncertain. Binding studies with the selective D2 receptor ligand [ 3 H]nemonapride have shown a small increase in the density of D2 receptors in the medial caudate/putamen, but not in the lateral caudate/putamen of PRS rats (Adrover et al, 2007). We could not find changes in striatal D1 and D2 receptor levels by immunoblot analysis in PRS rats .…”

Section: Discussioncontrasting

confidence: 77%

Early Life Stress Causes Refractoriness to Haloperidol-Induced Catalepsy

et al. 2013

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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 1 neurons in the external and internal globus pallidus, subthalamic nucleus, and ventral motor thalamic nuclei. Remarkably, the number of c-Fos 1 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.

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Section: Discussioncontrasting

confidence: 77%

Early Life Stress Causes Refractoriness to Haloperidol-Induced Catalepsy

et al. 2013

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“…We also found that prenatal stress (PS) increased D2 receptors both in the left and right sides of NAc but the left-right asymmetries observed in the control groups were selectively lost in adult rats exposed to PS. Medial caudate putamen (CPu-M) showed an increased of D2 receptors after PS in both hemispheres and asymmetries in both control and stressed groups (Adrover et al 2007). We also observed a decrease of amphetamine stimulated DA dialysate in prefrontal cortex of PS rats at postnatal day (PND) 60 compared with controls (Katunar et al 2008).…”

Section: Introductionmentioning

confidence: 54%

Ontogenetic Expression of Dopamine-Related Transcription Factors and Tyrosine Hydroxylase in Prenatally Stressed Rats

et al. 2009

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The development of the central nervous system can be permanently affected by insults received during the perinatal period, predisposing the organism to long-term behavioral and neurochemical abnormalities. Rats exposed to different types of stress during the last week of gestation produce offspring that show several alterations, many of which have been attributed to changes in dopamine (DA) neurotransmission that could serve as the neurochemical basis for the development of neuropsychiatric disorders. Employing an immunocytochemical approach, we studied the expression levels of two transcription factors Nurr1 and Pitx3 which are expressed at critical moments of DA neurons differentiation as well as the expression of the rate limiting enzyme in DA synthesis, tyrosine hydroxylase (TH) in mesencephalic areas of the brains of prenatally stressed (PS) offspring at different postnatal ages. Main results show that stress exerted to the gestant mother produces permanent effect in the ontogenetic expression of key factors related to the DA metabolism mainly in the ventral tegmental area (VTA) of the mesencephalon. The immunocytochemical expression of the transcription factor Nurr1 shows an increase at postnatal days (PNDs) 7, 28, and 60 whereas Pitx3 shows a decrease at PND 28 and an increase at 60 PND. The rate limiting step in DA synthesis, the enzyme TH shows a decrease at PND 7 to reach control levels at PNDs 28 and 60. The increase of TFs might be up-regulating TH in order to restore DA levels that were previously seen to be normal before puberty. The area selectivity of the increase of the TFs toward VTA and the mesolimbic pathway indicates that an insult received during the prenatal period will exert mainly motivational, emotional, and reward behavior impairments in the adult life.

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“…Asymmetries in human neurotransmitters (including dopamine) were first documented several decades ago (Glick et al, 1982), and asymmetries in rodent dopaminergic systems can have functional relevance at molecular and behavioral levels (e.g., Adrover et al, 2007; Besson and Louilot, 1995; Louilot and Le Moal, 1994). Particularly relevant to the present work is a study suggesting that the NAc dopaminergic response to appetitive odors is differentially lateralized as a function of the animal’s conditioning history (Besson and Louilot, 1995).…”

Section: Discussionmentioning

confidence: 99%