Acquisition, steady-state performance, and the effects of trimethyltin on the operant behavior and hippocampal GFAP of Long–Evans and Fischer 344 rats

Abstract

Strain differences represent an overlooked variable that may play an important role in neurotoxic outcomes that can impact regulatory decision making. Here, we examined the strain-dependent effects of trimethyltin (TMT), a compound used as a positive control for behavioral and neurochemical assessments of neurotoxicity. Adult male Long–Evans (LE) and Fischer 344 (F344) rats ( n=12 each) were trained to respond under a multiple, fixed-interval 3-min fixed-ratio 10-response (multi FI 3-min FR10) schedule of milk reinforcement. Acquisition was characterized by time-dependent changes in several behavioral endpoints in both strains, although rate of acquisition of the fixed-interval pattern of responding was slower in F344 rats. Steady-state (baseline) performance was characterized by slower overall rates of responding in F344 rats. There was little evidence of strain differences in many of the other baseline performance measures. Rats of each strain were then divided into two equal groups that received either 1 ml/kg saline or 8.0 mg/kg iv TMT approximately 18 h before the next test session. TMT produced transient changes in the performance of LE and F344 rats that lasted for several sessions. For many behavioral measures, F344 rats were more affected by TMT than were LE rats. TMT-induced reactive gliosis, as assessed by assaying glial fibrillary acidic protein (GFAP), was also greater in F344 rats than in LE rats. These results suggest F344 rats may be more susceptible to TMT-induced neurotoxicity than are LE rats.