Adenylyl cyclase signal transduction and alcohol-induced sedation

Janice Froehlich, Gary S. Wand

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

This study examined adenylyl cyclase (AC) signal transduction in alcohol-sensitive brain regions of rats selectively bred for high (HAD) and low (LAD) alcohol drinking and correlated these findings with differences in sensitivity and tolerance to alcohol-induced sedation found within these lines. LAD rats were more sensitive to the sedative effects of alcohol than were HAD rats as evidenced by a shorter latency to lose the righting response (RR) after a single alcohol challenge. When time to recover the RR was compared after each of two alcohol challenges, HAD rats recovered the RR more rapidly following the second challenge compared to the first, indicating that the HAD rats rapidly developed tolerance to the sedative effects of alcohol. Tolerance did not develop in rats of the LAD line. Two months after completion of behavioral testing, adenylyl cyclase (AC) signal transduction was examined in alcohol-sensitive brain regions of rats from both lines. Immunoblot analyses indicated that LAD rats had greater G(s)α expression in the frontal cortex (FC) and hippocampus (HIP) compared to HAD rats. Rats with the highest HIP and FC G(s)α. levels were more rapidly affected by the sedative properties of alcohol than were rats with lower G(s)α levels. G protein expression and AC activity in the FC, RIP, cerebellum (CERE), and nucleus accumbens (ACE) were also correlated with sensitivity to the sedative properties of alcohol and with the rapid development of tolerance to this alcohol effect. The results suggest that sensitivity and tolerance to alcohol-induced sedation may be mediated in part through AC signal transduction.

Original languageEnglish
Pages (from-to)1021-1030
Number of pages10
JournalPharmacology Biochemistry and Behavior
Volume58
Issue number4
DOIs
StatePublished - Dec 1997

Fingerprint

Signal transduction
Adenylyl Cyclases
Signal Transduction
Rats
Alcohols
Righting Reflex
Hypnotics and Sedatives
Frontal Lobe
Hippocampus
Brain
Nucleus Accumbens
GTP-Binding Proteins
Alcohol Drinking
Cerebellum

Keywords

  • Adenylyl cyclase
  • Alcohol drinking
  • Alcohol sensitivity
  • Alcohol tolerance
  • cAMP
  • G proteins
  • Genetic selection

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Adenylyl cyclase signal transduction and alcohol-induced sedation. / Froehlich, Janice; Wand, Gary S.

In: Pharmacology Biochemistry and Behavior, Vol. 58, No. 4, 12.1997, p. 1021-1030.

Research output: Contribution to journalArticle

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