Involvement of nigral oxytocin in locomotor activity: A behavioral, immunohistochemical and lesion study in male rats

Laura Angioni,Cristina Cocco,Gian-Luca Ferri,Antonio Argiolas,Maria Rosaria Melis,Fabrizio Sanna

doi:10.1016/j.yhbeh.2016.05.012

Laura Angioni, Cristina Cocco + Show 4 more

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https://doi.org/10.1016/j.yhbeh.2016.05.012

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Journal: Hormones and Behavior	Publication Date: May 14, 2016
Citations: 29	License type: cc-by

Affiliation: University of Cagliari

Abstract

Oxytocin is involved in the control of different behaviors, from sexual behavior and food consumption to empathy, social and affective behaviors. An imbalance of central oxytocinergic neurotransmission has been also associated with different mental pathologies, from depression, anxiety and anorexia/bulimia to schizophrenia, autism and drug dependence. This study shows that oxytocin may also play a role in the control of locomotor activity. Accordingly, intraperitoneal oxytocin (0.5–2000μg/kg) reduced locomotor activity of adult male rats. This effect was abolished by d(CH2)5Tyr(Me)2-Orn8-vasotocin, an oxytocin receptor antagonist, given into the lateral ventricles at the dose of 2μg/rat, which was ineffective on locomotor activity. Oxytocin (50–200ng/site) also reduced and d(CH2)5Tyr(Me)2-Orn8-vasotocin (2μg/site) increased locomotor activity when injected bilaterally into the substantia nigra, a key area in the control of locomotor activity. Conversely, the destruction of nigral neurons bearing oxytocin receptors by the recently characterized neurotoxin oxytocin-saporin injected into the substantia nigra, increased basal locomotor activity. Since oxytocin-saporin injected into the substantia nigra caused a marked reduction of neurons immunoreactive for tyrosine hydroxylase (e.g., nigrostriatal dopaminergic neurons) and for vesicular glutamate transporters VGluT1, VGluT2 and VGluT3 (e.g., glutamatergic neurons), but not for glutamic acid decarboxylase (e.g., GABAergic neurons), together these findings suggest that oxytocin influences locomotor activity by acting on receptors localized presynaptically in nigral glutamatergic nerve terminals (which control the activity of nigral GABAergic efferent neurons projecting to brain stem nuclei controlling locomotor activity), rather than on receptors localized in the cell bodies/dendrites of nigrostriatal dopaminergic neurons.

Highlights

Oxytocin, the neurohypophyseal hormone well known for its hormonal role in lactation and parturition, exerts widespread actions in central nervous system
The substantia nigra is a brain area of special interest since: 1) oxytocinergic fibres and terminals project here from the paraventricular nucleus of the hypothalamus (Adan et al, 1995; Mai et al, 1993; Sofroniew, 1983; Zimmerman et al, 1984); 2) oxytocinergic receptors and oxytocin receptor messenger RNA are found in the substantia nigra of the human (Loup et al, 1989, 1991) and rat brain (Vaccari et al, 1998), respectively; and 3) the pars compacta of the substantia nigra contains the cell bodies of nigrostriatal dopaminergic neurons which project to the basal ganglia, in circuits playing a pivotal role in the control of motor activity
In particular our results confirm that oxytocin decreases locomotor activity of male rats in a non-novelty paradigm when given IP at high doses (2 mg/kg), but not at doses up to 0.05 mg/kg, which were found ineffective when compared to vehicle-treated control rats

Summary

Introduction

The neurohypophyseal hormone well known for its hormonal role in lactation and parturition, exerts widespread actions in central nervous system. Angioni et al / Hormones and Behavior 83 (2016) 23–38 system, which plays a key role in the control of locomotor activity In this regard, the substantia nigra is a brain area of special interest since: 1) oxytocinergic fibres and terminals project here from the paraventricular nucleus of the hypothalamus (Adan et al, 1995; Mai et al, 1993; Sofroniew, 1983; Zimmerman et al, 1984); 2) oxytocinergic receptors and oxytocin receptor messenger RNA are found in the substantia nigra of the human (Loup et al, 1989, 1991) and rat brain (Vaccari et al, 1998), respectively; and 3) the pars compacta of the substantia nigra contains the cell bodies of nigrostriatal dopaminergic neurons which project to the basal ganglia, in circuits playing a pivotal role in the control of motor activity (see von Bohlen Und Halbach et al, 2004). The degeneration of dopaminergic nigrostriatal neurons causes motor disturbances such as those found in Parkinson's disease (see Hodaie et al, 2007)

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