The effect of age on the discriminative stimulus effects of ethanol and its GABAA receptor mediation in cynomolgus monkeys
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Excessive alcohol consumption is less common among aged compared to young adults, with aged adults showing greater sensitivity to many behavioral effects of ethanol.
This study compared the discriminative stimulus effects of ethanol in young and middle-aged adult cynomolgus monkeys (Macaca fascicularis) and its γ-aminobutyric acid (GABA)A receptor mediation.
Two male and two female monkeys trained to discriminate ethanol (1.0 g/kg, i.g.; 60-min pre-treatment interval) from water at 5–6 years of age (Grant et al. in Psychopharmacology 152:181–188, 2000) were re-trained in the current study more than a decade later (19.3 ± 1.0 years of age) for a within-subjects comparison. Also, four experimentally naïve middle-aged (mean ± SEM, 17.0 ± 1.5 years of age) female monkeys were trained to discriminate ethanol for between-subjects comparison with published data from young adult naïve monkeys.
Two of the naïve middle-aged monkeys attained criterion performance, with weak stimulus control and few discrimination tests, despite greater blood–ethanol concentration 60 min after 1.0 g/kg ethanol in middle-aged compared to young adult female monkeys (Green et al. in Alcohol Clin Exp Res 23:611–616, 1999). The efficacy of the GABAA receptor positive modulators pentobarbital, midazolam, allopregnanolone, pregnanolone, and androsterone to substitute for the discriminative stimulus effects of 1.0 g/kg ethanol was maintained from young adulthood to middle age.
The data suggest that 1.0 g/kg ethanol is a weak discriminative stimulus in naive middle-aged monkeys. Nevertheless, the GABAA receptor mechanisms mediating the discriminative stimulus effects of ethanol, when learned as a young adult, appear stable across one third of the primate lifespan.
KeywordsEthanol Discrimination Monkey Aging GABA receptor
This research was supported by RR000163, NIH/NIAAA AA013510, AA13541, AA017040, and NIH/NIA AG023477.
- Center for Disease Control and Prevention (2010) Vital and health statistics. Health behaviors of adults: United States 2005–2007. US Department of Health and Services, Washington, DC, Series 10, No. 245; DHHS Publication No. (PHS) 2010-1573Google Scholar
- Grant BF, Dawson DA, Stinson FS, Chou P, Dufour MC, Pickering RP (2006) The 12-month prevalence and trends in DSM-IV alchol abuse and dependence: United States, 1991–1992 and 2001–2002. Alcohol Res Health 29:79–993Google Scholar
- Groerer JC, Penne MA, Pemberton MR, Folsom RE (2003) Substance abuse treatment need among older adults in 2020: the impact of the aging baby-boom cohort. Drug Alcohol Abuse 69:127–135Google Scholar
- Kanaumi T, Takashima S, Iwasaki H, Mitsudome A, Hirose S (2006) Developmental changes in the expression of GABAA receptor alpha 1 and gamma 2 subunits in human temporal lobe, hippocampus and basal ganglia: an implication for consideration on age related epilepsy. Epilepsy Res 71:47–53Google Scholar
- National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington, p 125Google Scholar
- Schumacher M, Weill-Engerer S, Liere P, Robert F, Franklin RJM, Garcia-Segura LM, Lambert JJ, Mayo W, Melcangi RC, Parducz A, Suter U, Carelli C, Baulieu EE, Akwa Y (2003) Steroid hormones and neurosteroids in normal and pathological aging of the nervous system. Prog Neurobiol 71:3–29PubMedCrossRefGoogle Scholar
- Central Intelligence Agency (2009) The World Factbook. https://www.cia.gov/library/publications/the-world-factbook/index.html Accessed 19 July 2010