Journal
SYNAPSE
Volume 63, Issue 11, Pages 972-981Publisher
WILEY
DOI: 10.1002/syn.20677
Keywords
substance P mRNA; central nucleus of the amygdala; alcohol preference; alcohol intake; anxiety
Categories
Funding
- National Institute on Alcohol Abuse and Alcoholism [AA10406, AA11555]
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In the present study, in vitro and in vivo studies were conducted to determine the relationship between innate substance P (SP) levels and alcohol-motivated behavior in alcohol-preferring (P) and nonpreferring (NP) rat lines. In Experiment 1, in situ hybridization and quantitative autoradiography were used to detect and measure SP mRNA levels in discrete brain loci of the P and NP rats. The results indicated significantly lower SP mRNA levels in the central nucleus of the amygdala (CeA) of P compared with those of NP rats. Experiment 2 evaluated the effects of SP, microinfused into the CeA, on alcohol (10%, v/v) and sucrose (2%, w/v) motivated responding in the P rat. The results revealed that, when infused into the CeA (1-8 mu g), SP reduced alcohol responding by 48-85% of control levels, with no effects on sucrose responding. Neuroanatomical control infusions (1-8 mu g) into the caudate putamen (CPu) also failed to significantly alter alcohol- or sucrose-motivated behaviors. Given the selective reductions on alcohol (compared to sucrose) responding by direct intracranial infusion of SP, the data suggest that deficits in SP signaling within the CeA (an anxiety regulating locus) are inversely associated with alcohol-motivated behaviors. Activation of SP receptors in the CeA may reduce anxiety-like behavior in the P rat and contribute to reductions on alcohol responding. The SP system may be a suitable target for the development of drugs to reduce alcohol-drinking behavior in humans. Synapse 63:972-981, 2009. (c) 2009 Wiley-Liss, Inc.
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