Tags

Type your tag names separated by a space and hit enter

Discriminative stimulus effects of ethanol in C57BL/6J and DBA/2J inbred mice.
Alcohol Clin Exp Res. 2002 Jun; 26(6):747-57.AC

Abstract

BACKGROUND

Two of the most widely used mouse strains for studying the behavioral effects of ethanol are C57BL/6J (B6) and DBA/2J (D2) mice. These strains exhibit marked differences in behavioral and physiological responses to ethanol. The subjective discriminative stimulus effects of ethanol may play a role in ethanol abuse, but the discriminative stimulus profile of ethanol has not been compared in B6 and D2 mice. Examination of the discriminative stimulus effects of ethanol in B6 and D2 mouse strains may enhance our understanding of the relationship between the subjective effects of ethanol and other ethanol-induced behavioral effects.

METHODS

Twelve adult male C57BL/6J mice and 12 male DBA/2J mice were trained to discriminate 1.5 g/kg ethanol from saline in daily 15 min, milk-reinforced operant sessions. After training, ethanol substitution and response-rate suppression dose response curves were determined for ethanol, midazolam, diazepam, pentobarbital, pregnanolone, 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), dizocilpine, and morphine.

RESULTS

D2 mice learned the ethanol discrimination significantly more quickly than did B6 mice. Ethanol, midazolam, pregnanolone, and dizocilpine fully substituted for ethanol in both strains. Pentobarbital was more potent in producing ethanol-like discriminative stimulus effects in D2 than B6 mice. Midazolam and diazepam were significantly more potent in suppressing response rates in D2 than B6 mice. Morphine failed to substitute for ethanol in either strain, but the ED50 for morphine suppression of responding was significantly lower in B6 than D2 mice.

CONCLUSIONS

The initial stimulus effects of 1.5 g/kg ethanol may be more salient in D2 than B6 mice. This does not appear to result from differences in the neurotransmitter systems that mediate ethanol's discriminative stimulus effects. In both strains, gamma-aminobutyric acid-positive modulators and a noncompetitive NMDA antagonist substituted for ethanol. However, strain differences did exist in the potency of gamma-aminobutyric acid-positive modulators and morphine for suppressing operant responding.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond 23298-0613, USA. klshelto@hsc.vcu.eduNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

12068241

Citation

Shelton, Keith L., and Kathleen A. Grant. "Discriminative Stimulus Effects of Ethanol in C57BL/6J and DBA/2J Inbred Mice." Alcoholism, Clinical and Experimental Research, vol. 26, no. 6, 2002, pp. 747-57.
Shelton KL, Grant KA. Discriminative stimulus effects of ethanol in C57BL/6J and DBA/2J inbred mice. Alcohol Clin Exp Res. 2002;26(6):747-57.
Shelton, K. L., & Grant, K. A. (2002). Discriminative stimulus effects of ethanol in C57BL/6J and DBA/2J inbred mice. Alcoholism, Clinical and Experimental Research, 26(6), 747-57.
Shelton KL, Grant KA. Discriminative Stimulus Effects of Ethanol in C57BL/6J and DBA/2J Inbred Mice. Alcohol Clin Exp Res. 2002;26(6):747-57. PubMed PMID: 12068241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus effects of ethanol in C57BL/6J and DBA/2J inbred mice. AU - Shelton,Keith L, AU - Grant,Kathleen A, PY - 2002/6/18/pubmed PY - 2002/11/26/medline PY - 2002/6/18/entrez SP - 747 EP - 57 JF - Alcoholism, clinical and experimental research JO - Alcohol Clin Exp Res VL - 26 IS - 6 N2 - BACKGROUND: Two of the most widely used mouse strains for studying the behavioral effects of ethanol are C57BL/6J (B6) and DBA/2J (D2) mice. These strains exhibit marked differences in behavioral and physiological responses to ethanol. The subjective discriminative stimulus effects of ethanol may play a role in ethanol abuse, but the discriminative stimulus profile of ethanol has not been compared in B6 and D2 mice. Examination of the discriminative stimulus effects of ethanol in B6 and D2 mouse strains may enhance our understanding of the relationship between the subjective effects of ethanol and other ethanol-induced behavioral effects. METHODS: Twelve adult male C57BL/6J mice and 12 male DBA/2J mice were trained to discriminate 1.5 g/kg ethanol from saline in daily 15 min, milk-reinforced operant sessions. After training, ethanol substitution and response-rate suppression dose response curves were determined for ethanol, midazolam, diazepam, pentobarbital, pregnanolone, 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), dizocilpine, and morphine. RESULTS: D2 mice learned the ethanol discrimination significantly more quickly than did B6 mice. Ethanol, midazolam, pregnanolone, and dizocilpine fully substituted for ethanol in both strains. Pentobarbital was more potent in producing ethanol-like discriminative stimulus effects in D2 than B6 mice. Midazolam and diazepam were significantly more potent in suppressing response rates in D2 than B6 mice. Morphine failed to substitute for ethanol in either strain, but the ED50 for morphine suppression of responding was significantly lower in B6 than D2 mice. CONCLUSIONS: The initial stimulus effects of 1.5 g/kg ethanol may be more salient in D2 than B6 mice. This does not appear to result from differences in the neurotransmitter systems that mediate ethanol's discriminative stimulus effects. In both strains, gamma-aminobutyric acid-positive modulators and a noncompetitive NMDA antagonist substituted for ethanol. However, strain differences did exist in the potency of gamma-aminobutyric acid-positive modulators and morphine for suppressing operant responding. SN - 0145-6008 UR - https://www.unboundmedicine.com/medline/citation/12068241/Discriminative_stimulus_effects_of_ethanol_in_C57BL/6J_and_DBA/2J_inbred_mice_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=2002&volume=26&issue=6&spage=747 DB - PRIME DP - Unbound Medicine ER -