Time-dependent deficits in delay conditioning produced by trimethyltin

Trimethylin (TMT) produces behavioral and cognitive deficits resulting, in part, from limbic system toxicity. To determine whether these effects result from learning deficits or accelerated memory loss, the present experiment examined two delay conditioning paradigms in rats previously treated with either saline or TMT. Saline-treated Long-Evans rats receiving injections of lithium after consuming saccharin-flavored water later avoided saccharin ingestion: the degree of avoidance varied inversely with the time (0.5, 3 or 6 h) separating initial saccharin availability and lithium injection. Rats treated with TMT (8 mg/kg IV, 30 days prior) showed impaired conditioning at the long but not the short or intermediate delay conditions, suggesting that the deficits were mnemonic and not associative. Similar delay-dependent deficits in rats treated with TMT were observed in a passive avoidance task that arranged one of two delays between response emission and shock delivery during training. The effects of TMT on delay conditioning were accompanied by reduced bodyweight and hippocampal pathology. In summary, TMT appears to alter the temporally dependent association of events (entering darkened compartment versus saccharin consumption) and consequences (foot shock versus lithium administration) during acquisition. Furthermore, the observed deficits in delay conditioning produced by TMT did not appear to be task specific, with similar effects determined with tests of both somatosensory and gustatory avoidance learning designed to distinguish between functional alterations due to deficits in memorial processes from those due to altered sensory, motor, or associative processes.Although the research described in this article has been supported by the United States Environmental Protection Agency (through contract 68-02-4450 to NSI — Environmental Sciences), it has not been subjected to Agency review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. A preliminary report of these data was given at the 1987 annual meeting of the Society of Toxicology, Washington, DC