Neuropeptide S Receptor Gene Expression in Alcohol Withdrawal and Protracted Abstinence in Postdependent Rats

Abstract

Background: Alcoholism is a chronic disease characterized by frequent intoxications followed by withdrawal episodes and relapse to alcohol use. Neuroplastic changes associated with these intoxication and withdrawal cycles are thought to play a key role in disease progression. Recently, it has been shown that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system, facilitates relapse to alcohol seeking in laboratory animals. Given that a history of ethanol intoxication may increase vulnerability to alcohol addiction, we sought to determine whether NPS receptor (NPSR) gene expression is altered during withdrawal.Methods: Rats were subjected to 1 week of intoxication by oral alcohol administration. NPSR gene expression was analyzed by in situ hybridization in rats 12 hours and 7 days after the last alcohol administration. To investigate the functional significance of NPSR system adaptation following protracted withdrawal 7 days after intoxication, we tested the anxiolytic-like properties of NPS in nondependent and postdependent rats using the shock probe defensive burying test (DB).Results: At both time points, increased NPSR gene expression was observed in several brain areas, including the endopiriform nucleus, the motor cortex, and the medial amygdaloid nucleus. Moderate increases in gene expression were also found in the lateral hypothalamus, paraventricular nucleus, basolateral and central amygdala. Differences from control animals were more pronounced after 7 days of abstinence. The upregulation of the NPSR system at this time point was confirmed by functional data indicating that intracerebroventricular (ICV) NPS administration (0.0, 0.3, and 0.1 nmol ⁄ rat) elicits more pronounced anxiolytic effects in postdependent animals than in controls subjected to the electric shock probe DB test.Conclusions: Neuropeptide S receptor mRNA expression is increased in different brain areas of postdependent rats; as shown in the DB test, this expression change is functionally relevant.

RETRACTED ARTICLE: Identification of gene expression profile in the rat brain resulting from acute alcohol intoxication

“…Recently, pathophysiology and etiology of acute alcohol intoxication through experimental practice on rodent models have gotten much attention, among which rat models have been universally adopted to discover the influence of acute alcohol intoxication on the central nervous system (CNS) [8,9]. Abundant rat models of acute alcohol intoxication have shown that acute alcohol intoxication may stimulate genetic expression of neural cells of the cerebellum, which may take significant part in the prognosis and treatment of CNS lesions [10,11].…”

Chronic Ethanol Potentiates the Effect of Neuropeptide S in the Basolateral Amygdala and Shows Increased Anxiolytic and Anti-Depressive Effects

“…This is supported by a recent study that demonstrated that chronic exposure to high levels of EtOH combined with a period of abstinence led to a significant upregulation of NPSR mRNA levels, both after acute EtOH withdrawal and after prolonged abstinence, in several brain regionsFincluding the BLA (Ruggeri et al, 2010). However, an increased NPS effect on mood may also reflect a change in neuronal excitability or neural network function in response to chronic EtOH consumption, unrelated to NPSR levels per se, that make the neuron/system more sensitive to NPSR activation.…”

Anatomical characterization of the neuropeptide S system in the mouse brain by in situ hybridization and immunohistochemistry

“…These observations suggest that NPS may play an important role in learning and memory. Other studies have produced evidence for a role of central NPS neurotransmission in reward and drug abuse (Badia-Elder et al, 2008;Canella et al, 2009;Pañeda et al, 2009;Ruggeri et al, 2010). Finally, we have recently described antipsychotic effects of NPS in animal models of pharmacologically induced psychosis (Okamura et al, 2010) and a possible genetic association of NPSR genotypes with panic disorder (Okamura et al, 2007).…”