The international journal of neuropsychopharmacology
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Int. J. Neuropsychopharmacol. · Aug 2014
Overexpression of Shati/Nat8l, an N-acetyltransferase, in the nucleus accumbens attenuates the response to methamphetamine via activation of group II mGluRs in mice.
A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens (NAc) of mice with methamphetamine (METH) treatment. Previously we reported that suppression of Shati/Nat8l enhanced METH-induced behavioral alterations via dopaminergic neuronal regulation. However, the physiological mechanisms of Shati/Nat8l on the dopaminergic system in the brain are unclear. ⋯ In the AAV vector-injected NAc, the tissue contents of both N-acetylaspartate and N-acetylaspartylglutamate (NAAG), endogenous mGluR3 agonist, were elevated. The injection of peptidase inhibitor of NAAG or the perfusion of NAAG itself reduced the basal levels of extracellular dopamine in the NAc of naive mice. These results indicate that Shati/Nat8l in the NAc, but not in the dS, plays an important suppressive role in the behavioral responses to METH by controlling the dopaminergic system via activation of group II mGluRs.
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Int. J. Neuropsychopharmacol. · Aug 2014
Cannabinoid modulation of predator fear: involvement of the dorsolateral periaqueductal gray.
The present study investigated the effects of systemic or intra-dorsolateral periaqueductal gray (dlPAG) administration of CB1 agonists on behavioural changes induced in rats by predator (a live cat) exposure, a model of panic responses. Since nitric oxide (NO) and cannabinoid neurotransmission are proposed to interact in the dlPAG to modulate defensive responses, we also investigated if NO is involved in the biphasic effects of anandamide (AEA) injected into the dlPAG. The results showed that systemic administration of WIN55,212-2 or intra-dlPAG AEA attenuated the defensive behaviours caused by cat exposure. ⋯ The cannabinoid receptor type 1 (CB1) antagonist AM251 prevented the panicolytic effect of AEA whereas a neuronal NOS inhibitor turned the ineffective high dose of AEA into an effective one. These results suggest that modulation of the cannabinoid system could be a target in the treatment of panic disorders. However, the biphasic effects of these compounds could limit their therapeutic potential.
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Int. J. Neuropsychopharmacol. · Aug 2014
SK channel blockade reverses cognitive and motor deficits induced by nigrostriatal dopamine lesions in rats.
Parkinson's disease has traditionally been viewed as a motor disorder caused by the loss of dopamine (DA) neurons. However, emotional and cognitive syndromes can precede the onset of the motor deficits and provide an opportunity for therapeutic intervention. Potassium channels have recently emerged as potential new targets in the treatment of Parkinson's disease. ⋯ The partial 6-OHDA lesions (56% striatal DA depletion) produced 20% decrease of iodinated apamin binding sites in the substantia nigra pars compacta in correlation with the loss of tyrosine hydroxylase positive cells, without modifying apamin binding in brain regions receiving DAergic innervation. Striatal extracellular levels of DA, not detectable after 6-OHDA lesions, were enhanced by apamin treatment as measured by in vivo microdialysis. These results indicate that blocking SK channels may reinstate minimal DA activity in the striatum to alleviate the non-motor symptoms induced by partial striatal DA lesions.
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Int. J. Neuropsychopharmacol. · Aug 2014
Corticosterone treatment during adolescence induces down-regulation of reelin and NMDA receptor subunit GLUN2C expression only in male mice: implications for schizophrenia.
Stress exposure during adolescence/early adulthood has been shown to increase the risk for psychiatric disorders such as schizophrenia. Reelin plays an essential role in brain development and its levels are decreased in schizophrenia. However, the relationship between stress exposure and reelin expression remains unclear. ⋯ CORT-induced reelin and GluN2C down-regulation in males was not associated with changes in two GABAergic neuron markers, GAD67 and parvalbumin, or glucocorticoids receptors (GR). These results show that CORT treatment causes long-lasting and selective reductions of reelin form levels in male FC and DH accompanied by changes in NMDAR subunit composition. This sex-specific reelin down-regulation in regions implicated in schizophrenia could be involved in the effects of stress in this disease.