Abstract
The Roman high(RHA) and low-Avoidance (RLA) rats were selectively bred for rapid vs poor acquisition of two-way active avoidance behavior. These lines differ in numerous behavioral traits, with RLA rats being more fearful/anxious than RHA rats, and the latter being novelty-seekers and showing larger intake of, and preference for, addictive substances including ethanol (ETH). Moreover, several differences in central dopaminergic, serotonergic, and GABAergic functions have been reported in these two lines. Since those neural systems are involved in the regulation of ETH consumption, it was considered of interest to investigate: 1) the differences in ETH intake and preference between RHA and RLA rats, 2) the effects of ETH on DA release in the shell of the nucleus accumbens (AcbSh) using brain microdialysis. ETH solutions of increasing concentrations (2% - 10%) were presented on alternate days in a free choice with water. To examine ETH intake and preference stability, animals were subsequently switched to daily presentations of 10% ETH for 10 consecutive days. RHA rats consumed significantly larger amounts of ETH and displayed higher ETH preference than did RLA rats throughout the acquisition and maintenance phases. Following chronic exposure to ETH the animals were habituated to a restricted access to ETH schedule (2% ETH, 2 h per day × 4 days) before surgical implantation of a dialysis probe in the AcbSh. Under these experimental conditions, voluntary ETH intake (2%, 1 h, p.o.) produced a significant increase in accumbal DA output in RHA rats but not in their RLA counterparts. Finally, the i.p. administration of ETH (0.25 g/kg) to na?ve Roman rats produced a significant increment in accumbal DA output only in RHA rats. These results indicate that the mesolimbic dopaminergic system of RHA rats is more responsive to the effects of ETH than that of RLA rats.
Highlights
Non selected outbred Wistar rats and heterogeneous stock rats (e.g., N/Nih) drink relatively small amounts of ethanol (ETH) voluntarily, considerable inter individual differences in the amounts of ETH consumed by these rats have been observed [1] [2]
Ethanol consumption during the acquisition phase. (a) Intake: Results are expressed as the mean ± S.E.M. daily ethanol (ETH) intake (g/kg) for concentrations ranging from 2% to 10%; (b) Preference: Shown are the mean and 95% confidence interval for daily ETH preference (%) for concentrations ranging from 2% to 10%
In order to clarify whether the lack of effect of voluntary oral ETH consumption on accumbal DA output in RLA rats was due to the lower ETH intake relative to that of their RHA counterparts, we investigated the effect of the non contingent i.p. administration of ETH at a dose of 0.25 g/kg, which is similar to the amount of ETH voluntarily consumed by RLA rats during the previous brain dialysis experiments
Summary
Non selected outbred Wistar rats and heterogeneous stock rats (e.g., N/Nih) drink relatively small amounts of ethanol (ETH) voluntarily, considerable inter individual differences in the amounts of ETH consumed by these rats have been observed [1] [2]. Taking advantage of such differences, some of which may be genetically determined, efforts have been made to develop animal models for studying the influence of genetic and environmental factors on the neural substrates of alcoholism. Line-related differences are observed in the response to rewarding stimuli, with RHA rats showing a greater intake of saccharin and ethanol under free choice conditions [10], a more robust activation of the mesolimbic dopaminergic system following the administration of different drugs of abuse [28] [29], as well as an increased ability to acquire intravenous cocaine self-administration and to reinstate drug-seeking behavior upon long term extinction [30]
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