High temporal resolution of amino acid levels in rat nucleus accumbens during operant ethanol self-administration: involvement of elevated glycine in anticipation.

Capillary electrophoresis coupled with laser-induced fluorescence detection (CE-LIF) provides 15-s temporal resolution of amino acid levels in microdialysate, which, for the first time, allows almost real time measurement of changes during episodes of behavior. We trained Sprague-Dawley rats to self-administer either 10% ethanol-containing gelatin or non-alcoholic gelatin in a typical operant chamber. After rats reached stable daily levels of responding, microdialysis probes were inserted into nucleus accumbens and samples were collected before, during and after operant sessions with on-line analysis via CE-LIF. During the first 15 min of the operant session, there was a significant increase in taurine that correlated with the amount of ethanol consumed (R(2)=0.81) but no change in rats responding for plain gel. There were large, consistent increases in glycine in both the ethanol and plain gel groups which correlated with the amount of gel consumed. A smaller increase was observed in rats with free non-operant access to plain gel compared to the increase seen with the same amount of gel consumed under operant conditions. When rats were given a time out after each delivery of gel in the operant protocol, the greatest increase of glycine was obtained with the longest time out period. Thus, increases in glycine in nucleus accumbens appear to be related to anticipation of reinforcement.

Intermittent high-dose ethanol exposures increase motivation for operant ethanol self-administration: possible neurochemical mechanism.

We investigated the neurochemical mechanism of how high-dose ethanol exposure may increase motivation for ethanol consumption. First, we developed an animal model of increased motivation for ethanol using a progressive ratio (PR) schedule. Sprague-Dawley rats were trained to administer 10% ethanol-containing gelatin or plain gelatin (on alternate weeks) in daily 30-min sessions under different fixed ratio (FR) and PR schedules. During FR schedules, rats self-administered about 1 g/kg ethanol, which was decreased to 0.4+/-0.03 g/kg under PR10. Rats then received four pairs of either 3 g/kg ethanol or saline injections during the weeks when the reinforcer was plain gelatin. During subsequent ethanol gel sessions, breakpoints and ethanol consumption rose 40% in the high-dose ethanol group by the fourth set of injections with no change in plain gel responding. Alterations in amino acids in the ventral striatum (VS) during PR10 responding for 10% ethanol gelatin and plain gelatin were measured using microdialysis sampling coupled with capillary electrophoresis and laser-induced fluorescence detection. There was greater release of taurine, glycine and glutamate in the NAC of the high-dose ethanol rats during 10% ethanol-containing gelatin responding, compared to the control rats or during plain gel responding. An increase in the release of glycine in this same brain region has recently been shown to be involved with anticipation of a reward. Thus, it appears that intermittent high-dose ethanol exposure not only increases motivation for ethanol responding but may also change neurotransmitter release that mediates anticipation of reinforcement, which may play a key role in the development of alcoholism.

Effects of an enrichment device on voluntary alcohol consumption on single-housed rats.

We evaluated the effect of an enrichment device (that is, a polyurethane bone) on the voluntary consumption of ethanol containing gel by single-housed rats. Male Sprague-Dawley rats (n = 5 per group) were exposed for 4 d to each of the following 3 treatments: access to a new synthetic bone and ethanol gel for 1 h daily (treatment 1); a new bone was left in the cage for 24 h, with access to ethanol gel for 1 h daily (treatment 2); and both the bone and ethanol gel remained in the cage for 24 h (treatment 3). Average alcohol consumption over 4 d was 0.86 +/- 0.13, 0.99 +/- 0.13, and 5.19 +/- 0.37 g/kg in the absence of the bone for treatments 1, 2, and 3, respectively, and 1.00 +/- 0.13, 0.620 +/- 0.07, and 5.55 +/- 0.38 g/kg with the bone for treatments 1, 2 and 3, respectively; none of these values differed significantly with regard to presence of the bone. During treatment 1, time spent with the synthetic bone was highest on the first 2 d, which altered the rate of ethanol consumption but not the total amount of ethanol consumed. During treatments 2 and 3, the rate and amount of ethanol consumption were comparable to basal levels. We conclude that adding an enrichment device that rats can chew and manipulate does not alter ethanol gel consumption. If used, environmental enrichment techniques should be evaluated during the research planning stages to avoid unintended alterations in the response to variables of interest.