ABSTRACT
We have adapted to mice a holeboard-learning task, which allows simultaneous assessment of spatial working and reference-memory performance. The holeboard apparatus consists of an open-field chamber with a 16-hole floor insert. Across trials, animals have to learn that the same four holes of 16 are always baited. Here, we show that C57BL/6 mice readily acquire this task within 4 days when submitted to six trials per day or within 8 days when submitted to only four trials per day. We also show that C57BL/6, Swiss-Webster, CD-1 and DBA/2 mice acquire this task similarly, despite the fact that some differences could be observed in measures of exploratory activity during habituation and training. Moreover, the muscarinic antagonist scopolamine disrupts learning at doses of 0.1 and 1.0 mg/kg, although the highest dose appeared to have side-effects. Lastly, we found that amyloid precursor protein transgenic mice have a selective disruption in their working-memory performance only during reversal training (i.e. after a change in the configuration of the baited holes). Overall, our data indicate that this spatial learning task is well adapted to mice and will be useful to characterize spatial memory in various genetic or pharmacological mouse models.
Subject(s)
Amyloid beta-Protein Precursor/physiology , Discrimination Learning/physiology , Exploratory Behavior/physiology , Memory, Short-Term/physiology , Spatial Behavior/physiology , Amyloid beta-Protein Precursor/genetics , Analysis of Variance , Animals , Discrimination Learning/drug effects , Dose-Response Relationship, Drug , Exploratory Behavior/drug effects , Genetics, Behavioral/methods , Male , Memory, Short-Term/drug effects , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Transgenic , Muscarinic Antagonists/administration & dosage , Reversal Learning/drug effects , Reversal Learning/physiology , Scopolamine/administration & dosage , Species Specificity , Statistics, NonparametricABSTRACT
BACKGROUND: The alcohol deprivation effect (ADE) is a temporary increase in the voluntary intake of ethanol solutions following a period of alcohol deprivation. Multiple deprivations can prolong the expression of an ADE. This study examined the effects of initial deprivation length, concurrent exposure to multiple ethanol concentrations, and number of deprivation exposures on the magnitude and duration of the ADE in alcohol-preferring (P) rats. METHODS: Adult female P rats received 24-hr free-choice access to 10, 20, and 30% ethanol and water for 6 weeks. Rats were then randomly assigned to three groups; one group served as a nondeprived control, whereas the other two groups were initially deprived of ethanol for 2 or 8 weeks. The ethanol solutions were restored to both deprived groups for 2 weeks before the groups were deprived of ethanol for another 2 weeks. This cycle was repeated three times for a total of four deprivations. RESULTS: After the initial ethanol deprivation period, both deprived groups displayed a similar 2-fold increased ethanol intake (g/Kg/day) during the initial 24-hr period when ethanol was restored. Both deprived groups showed greater than 2-fold increases in intake of the 20 and 30% ethanol solutions after re-exposure. Ethanol consumption returned to baseline levels within 2 weeks, before the subsequent deprivation period. Multiple deprivations increased the magnitude of the ADE over that observed in the first deprivation during the initial 24-hr period of re-exposure and prolonged the duration of the ADE. In addition, repeated deprivations increased ethanol intake in the first 2-hr period of re-exposure and produced blood ethanol levels in excess of 150 mg/100 ml. CONCLUSIONS: Alterations in the reinforcing and/or aversive effects of alcohol occurred after a single prolonged deprivation and were enhanced with repeated deprivations.
