Conditioned taste aversions as a behavioral baseline for drug discrimination learning: an assessment with phencyclidine.

When PCP was given prior to the pairing of saccharin with LiCl (and the PCP vehicle prior to a nonpoisoned exposure to the same saccharin solution), rats rapidly acquired the discrimination, avoiding saccharin consumption following PCP and consuming saccharin following the vehicle after only three conditioning trials. Conversely, when the PCP vehicle was given prior to the saccharin-LiCl pairing and PCP prior to a nonpoisoned exposure to saccharin, other subjects avoided saccharin consumption following the vehicle injection and readily consumed saccharin after an injection of PCP. During dose substitution sessions, animals displayed greater drug-appropriate responding as the dose of PCP increased. When a range of doses of ketamine was given in place of PCP prior to saccharin access, subjects displayed dose-dependent PCP-appropriate responding. When a range of doses of d-amphetamine was substituted for PCP, subjects displayed vehicle-appropriate responding at all doses. The relative efficacy of the taste aversion procedure as a baseline for drug discrimination learning is discussed.

Effects of trimethyltin chloride on the LiCl dose-response function for conditioned taste aversions in rats.

Twenty-one days following intragastric administration of 6.0 mg/kg of TMT (TMT chloride base/kg) or equivolume distilled water, groups of rats were injected with various doses of LiCl (0, 0.15, 0.60 or 1.8 mEq/kg) following the consumption of a novel saccharin solution. Both groups subsequently avoided the consumption of saccharin, with the degree of the aversion directly related to the dose of LiCl. Further, there was no difference between the TMT- and non-TMT-treated rats in the degree of aversion at any dose. These data suggest that the previously-reported effect of TMT on long-delay taste aversion learning was not likely due to changes in sensory responsiveness.

Effects of trimethyltin chloride on differential-reinforcement-of-low-rate responding.

The effects of a range of doses of trimethyltin chloride (1.8-7.0 mg/kg, TMT) on responding maintained under a differential-reinforcement-of-low-rate 15-sec schedule of water presentation were examined in rats. TMT produced a large decrease in the percent of reinforced responses and consequently a decrease in the rate of reinforcement. These effects were due primarily to prolonged bursts of nonreinforced responses. In contrast to the gradual dose-related decrease in body weight produced by TMT, responding was disrupted only at the highest dose tested, i.e., 7.0 mg/kg. The results were discussed in terms of the neurotoxic effects of TMT on the limbic system.

The effects of trimethyltin chloride on the acquisition of long delay conditioned taste aversion learning in the rat.

Naive rats injected with LiCl at various times following consumption of a novel saccharin solution subsequently avoided the ingestion of saccharin with the degree of the aversion related to the interval between ingestion and LiCl administration. Although a similar relationship was also evident in animals which had received a single intragastric administration of trimethyltin chloride 21 days prior to the pairing of saccharin and LiCl, the trimethyltin-pretreated subjects receiving delayed injections of LiCl displayed weaker taste aversions than those not exposed to trimethyltin. This disruption in the acquisition of taste aversions over long delays is consistent with other work suggesting that trimethyltin disrupts tasks involving short-term memory. The utility of the conditioned taste aversion paradigm in detecting and characterizing drug toxicity was discussed.

Sex differences in taste aversion learning: an analysis of the minimal effective dose.

Male and female rats injected with various doses of LiCl following the consumption of a novel saccharin solution subsequently avoided consumption of saccharin, with the degree of the aversion directly related to the dose of LiCl. Although this dose-response relationship was evident for both males and females, the minimal effective dose for inducing an aversion was lower for males, an effect consistent with previous work examining sex differences in taste aversion learning. The necessity of considering sex as a variable when comparing the relative sensitivity of behavioral measures of toxicity was discussed.