Effect of early rearing conditions on alcohol drinking and 5-HT1A receptor function in C57BL/6J mice.
We have evaluated in C57BL/6J mice the effect of maternal separation and post-weaning social isolation on ethanol intake, and on serotonin1A (5-HT1A) receptor function at the level of receptor-G protein interaction in the hippocampus and dorsal raphe nucleus. From postnatal days 2-14, litters were separated from the mother for 15 min (Handled) or for 180 min (Maternal separation). After weaning, pups were housed in pairs or in social isolation. At 2 months of age, ethanol intake and preference in mice were assessed using the two-bottle choice paradigm. Maternal separation increased ethanol preference in female mice that were subsequently housed in isolation. By contrast, post-weaning isolation increased ethanol preference and consumption in male mice regardless of pre-weaning rearing conditions. The increased ethanol preference and intake were limited to a 5% (v/v) concentration of ethanol. Our data suggest that adolescent mice are susceptible to the effects of post-weaning social isolation as shown by increased ethanol preference and consumption. Using quantitative autoradiography, 5-HT1A receptor number and function were determined by the binding of [3H]WAY-100635, and by [35S]GTPgammaS binding stimulated by the 5-HT1A receptor agonist 8-OH-DPAT, respectively. The binding experiments were done at approximately 3 months after the end of the two-bottle choice test in an attempt to minimize direct effects of ethanol drinking on 5-HT1A receptor function and number. 5-HT1A receptor-stimulated [35S]GTPgammaS binding in the dorsal raphe nucleus was increased in animals reared after weaning in isolation vs. in pairs, regardless of gender or pre-weaning rearing conditions. Our data suggest that there are long-term neurochemical consequences of social isolation of adolescent mice, specifically increased 5-HT1A receptor function in the dorsal raphe nucleus.
Advani
Tushar
T
Department of Pharmacology, University of Texas Health Science Center-San Antonio, San Antonio, TX 78229-3900, USA.
Hensler
Julie G
JG
Koek
Wouter
W
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D007554:Isotopes / Q000493:pharmacokinetics; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D012737:Sex Factors; D012934:Social Isolation; D013997:Time Factors
D007554:Isotopes; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide