TRH antagonism of ethanol sedation was evaluated in selectively-bred alcohol-preferring (P) and -nonpreferring (NP) rats. Intracerebroventricular (i.c.v.) infusions of TRH significantly reduced sleep time in the NP rats. In the P rats, TRH tended to reduce sleep, but this reduction was not significant. TRH had no significant effect on peripheral blood alcohol concentrations. The present results show that NP rats are more sensitive to the analeptic effect of TRH compared to P rats. These data support and extend those of others who have demonstrated a TRH antagonism on drug-induced sedation. Differential sensitivity to TRH may reflect differences in TRH receptor activity and/or TRH metabolism. Sensitivity to TRH analepsis may be associated with sensitivity to ethanol.
机构:
Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, S-17176 Stockholm, Sweden
Uppsala Univ, Dept Pharmaceut Biosci, Drug Safety & Toxicol, S-75124 Uppsala, Sweden
Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USAKarolinska Inst, Dept Clin Neurosci, Ctr Mol Med, S-17176 Stockholm, Sweden
Karlsson, Oskar
Colombo, Giancarlo
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Natl Res Council Italy, Neurosci Inst, Sect Cagliari, I-09042 Monserrato, CA, ItalyKarolinska Inst, Dept Clin Neurosci, Ctr Mol Med, S-17176 Stockholm, Sweden
Colombo, Giancarlo
Roman, Erika
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Uppsala Univ, Dept Pharmaceut Biosci, Unit Neuropharmacol Addict & Behav, S-75124 Uppsala, SwedenKarolinska Inst, Dept Clin Neurosci, Ctr Mol Med, S-17176 Stockholm, Sweden