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Titolo:
Genetic correlations between initial sensitivity to ethanol and brain cAMPsignaling in inbred and selectively bred mice
Autore:
Kirstein, SL; Tabakoff, B;
Indirizzi:
Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA Univ Colorado Denver CO USA 80262 r, Dept Pharmacol, Denver, CO 80262 USA
Titolo Testata:
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
fascicolo: 6, volume: 25, anno: 2001,
pagine: 791 - 799
SICI:
0145-6008(200106)25:6<791:GCBIST>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED MOTOR INCOORDINATION; GENOTYPIC CORRELATIONS; BEHAVIORAL-RESPONSES; FUNCTIONAL TOLERANCE; ADENYLATE-CYCLASE; MOUSE LINES; DROSOPHILA; SENSITIZATION; STOICHIOMETRY; HYPOTHERMIA;
Keywords:
ethanol; cAMP signaling; initial sensitivity; tolerance; mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Tabakoff, B Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, 4200 E 9th Ave,POB C-236, Denver, CO 80262 USA Univ Colorado 4200 E 9th Ave,POB C-236 DenverCO USA 80262 USA
Citazione:
S.L. Kirstein e B. Tabakoff, "Genetic correlations between initial sensitivity to ethanol and brain cAMPsignaling in inbred and selectively bred mice", ALC CLIN EX, 25(6), 2001, pp. 791-799

Abstract

Background: Several lines of evidence have suggested a role for cAMP (adenosine 3 ' ,5 ' -cyclic monophosphate) signaling in the acute and chronic effects of ethanol. This study investigated whether there is a genetic correlation between cAMP synthesis in the brain and the acute effects of ethanol [alcohol sensitivity or acute functional tolerance (AET)]. Methods: By using nine inbred strains of mice, we measured initial sensitivity and AFT to ethanol with a test of balance on a dowel. Initial sensitivity was defined by the blood ethanol concentration (BEC0) at the loss of balance on a dowel after an ethanol injection [1.75 g/kg intraperitoneally (ip)]. When mice were able to regain balance on the dowel, BEG, was determined, and a second ethanol injection was given (2 g/kg ip). Upon final regaining of balance, BEG, was determined. AFT was defined by the difference between BEC1 and BEC2 (AFT = Delta BEC = BEC2 - BEC1). Cyclic AMP synthesis was measured in whole-cell preparations in the cerebellum and other brain areasof mice of the nine inbred strains. Results: Significant differences in BEG, and AET were seen among the mice of the nine inbred strains. Cerebellar basal and forskolin- and isoproterenol-stimulated cAMP production differed significantly between the strains, and BEG, was found to correlate significantly with forskolin- and isoproterenol-stimulated cAMP accumulation in the cerebellum (r = 0.70 and 0.94, respectively). When we measured cAMP production in mesencephalic and telencephalic tissue in three strains of mice that differed significantly in isoproterenol-stimulated cAMP accumulation in the cerebellum, significant differences between strains were found only in telencephalic tissue. The relative relationship between the rank order of the three strains for cAMP accumulation in the telencephalon and initial sensitivity to ethanol was identical to that seen with the cerebellum However, AFT did not correlate with cAMP accumulation in the cerebellum or any other brain area tested. Conclusions: These results suggest that cAMP-generating systems of the cerebellum and possibly the brain areas contained in telencephalic tissues (e.g., basal ganglia) may have an important relationship to an animal's initial sensitivity to the incoordinating effects of ethanol.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 05:09:18