The effect of age on the discriminative stimulus effects of ethanol and its GABAA receptor mediation in cynomolgus monkeys
- Christa M. HelmsAffiliated withDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University Email author
- , Kathleen A. GrantAffiliated withDepartment of Behavioral Neuroscience, Oregon Health & Science UniversityDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University
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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
- The effect of age on the discriminative stimulus effects of ethanol and its GABAA receptor mediation in cynomolgus monkeys
Volume 216, Issue 3 , pp 333-343
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- 2. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR, 97006-6448, USA
- 1. Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA