Neuropeptide S receptor gene expression in alcohol withdrawal and protracted abstinence in postdependent rats.
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.
Department of Experimental Medicine and Public Health, University of Camerino, Camerino, Italy.
Barbara
B
Ruggeri
Simone
S
Braconi
Nazzareno
N
Cannella
Marsida
M
Kallupi
Laura
L
Soverchia
Roberto
R
Ciccocioppo
Massimo
M
Ubaldi
D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage; D005786:Gene Expression Regulation; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000378:metabolism*; D013695:Temperance; D013997:Time Factors
C484532:NPSR1 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000431:Ethanol