Angioni Laura, Cocco Cristina, Ferri Gian-Luca, Argiolas Antonio, Melis Maria Rosaria, Sanna Fabrizio
Department of Biomedical Sciences, Section of Cytomorphology, NEF Laboratory, University of Cagliari, 09042 Monserrato (Cagliari), Italy.
Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, Neuropsychobiology Laboratory, University of Cagliari, 09042 Monserrato (Cagliari), Italy.
Horm Behav. 2016 Jul;83:23-38. doi: 10.1016/j.yhbeh.2016.05.012. Epub 2016 May 14.
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)-Orn(8)-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)-Orn(8)-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.
催产素参与多种不同行为的调控，包括性行为、食物摄取以及共情、社交和情感行为等。中枢催产素能神经传递失衡还与多种精神疾病相关，如抑郁症、焦虑症、厌食症/贪食症、精神分裂症、自闭症和药物依赖等。本研究表明，催产素在运动活动的调控中可能也发挥作用。相应地，腹腔注射催产素（0.5 - 2000μg/kg）可降低成年雄性大鼠的运动活动。侧脑室注射剂量为2μg/大鼠的催产素受体拮抗剂d(CH2)5Tyr(Me)(2)-Orn(8)-血管紧张素可消除此效应，该拮抗剂对运动活动无影响。当双侧注射到黑质（运动活动控制的关键区域）时，催产素（50 - 200ng/部位）也会降低运动活动，而d(CH2)5Tyr(Me)(2)-Orn(8)-血管紧张素（2μg/部位）则会增加运动活动。相反，向黑质注射最近鉴定出的神经毒素催产素 - 皂草素破坏表达催产素受体的黑质神经元后，基础运动活动增加。由于向黑质注射催产素 - 皂草素会导致酪氨酸羟化酶免疫反应阳性神经元（如黑质纹状体多巴胺能神经元）以及囊泡谷氨酸转运体VGluT1、VGluT2和VGluT3免疫反应阳性神经元（如谷氨酸能神经元）显著减少，但谷氨酸脱羧酶免疫反应阳性神经元（如γ-氨基丁酸能神经元）不受影响，综合这些发现表明，催产素通过作用于黑质谷氨酸能神经末梢突触前定位的受体（这些神经末梢控制投射到控制运动活动的脑干核团的黑质γ-氨基丁酸能传出神经元的活动）来影响运动活动，而非作用于黑质纹状体多巴胺能神经元的细胞体/树突中定位的受体。
