Effects of ethanol and GABAB drugs on working memory in C57BL/6J and DBA/2J mice
- 163 Downloads
It has been suggested that GABAB receptors may be part of a neural substrate mediating some of the effects of ethanol.
The purpose of this experiment was to investigate, in mice, the effects of ethanol on working memory in a delayed matching-to position (DMTP) task, and additionally to determine if these effects were modulated by GABAB receptors.
Female C57BL/6J and DBA/2J mice were trained in the DMTP task, and after asymptotic levels of performance accuracy were achieved, injections (IP) of ethanol, baclofen, or phaclofen were administered. Baclofen or phaclofen were then co-administered with ethanol. Each test was repeated twice.
Ethanol caused deficits in working memory at 2.0 g/kg and higher. The highest dose (2.5 g/kg) produced additional non-specific effects, indicative of sedation. Baclofen increased performance accuracy (2.5 mg/kg), while decreasing the total number of trials completed. When combined with ethanol (1.5 g/kg), baclofen increased memory deficits at the highest dose (7.5 mg/kg). Phaclofen increased performance accuracy at 10 and 30 mg/kg but had no effect on the total number of trials completed. When combined with ethanol (2.5 g/kg), phaclofen did not significantly alter ethanol-induced deficits in performance.
Analyses of performance accuracy, total trials completed and variables indexing bias and motor impairment indicated that GABAB drugs modulate working memory in a behaviorally specific manner. Overall, these receptors may be part of a neural substrate that modulates some of the effects of ethanol.
KeywordsGABAB Ethanol Alcohol DMTP Working memory Mice
- Broadbent J, Harless WE (1999) Differential effects of GABAA and GABAB agonists on sensitization to the locomotor stimulant effects of ethanol in DBA/2J mice. Psychopharmacology 141:197–205Google Scholar
- Crabbe JC, Belknap JK, Buck KJ, Metten P (1994) Use of recombinant inbred strains for studying genetic determinants of responses to alcohol. Alcohol Alcohol 2:67–71Google Scholar
- Dunnett SB (1985) Comparative effects of cholinergic drugs and lesions of nucleus basalis or fimbria-fornix on delayed matching in rats. Psychopharmacology 87:357–363Google Scholar
- Humeniuk RE, White JM, Ong J (1993) The role of GABAB receptors in mediating the stimulatory effects of ethanol in mice. Psychopharmacology 111:219–224Google Scholar
- Mead AJ, Little HJ (1995) Do GABAB receptors have a role in causing behavioral hyperexcitability, both during ethanol withdrawal and in naive mice? Psychopharmacology 117:232–239Google Scholar
- Sahgal A (1987a) Contrasting effects of vasopressin, desglycinamide-vasopressin and amphetamine on a delayed matching to position task in rats. Psychopharmacology 93:243–249Google Scholar
- Winer BJ, Brown DR, Michels KM (1991) Statistical principles in experimental design, 3rd edn. McGraw-Hill, BostonGoogle Scholar