Time-dependent deficits in delay conditioning produced by trimethyltin

Abstract

Trimethyltin (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.

Cognitive Function

“…Peele et al (1989) exposed rats to trimethyltin (TMT) and assessed them 30 d later for conditioned flavor aversions to saccharin by pairing it with lithium chloride, which induces nausea. Peele et al (1989) exposed rats to trimethyltin (TMT) and assessed them 30 d later for conditioned flavor aversions to saccharin by pairing it with lithium chloride, which induces nausea.…”

Ethological and Experimental Approaches to Behavior Analysis: Implications for Ecotoxicology

“…This separation of the flavor from the noxious agent has allowed further exploration of the variables affecting flavor-aversion conditioning. Peele et al (54), for example, also studied the effect of the neurotoxicant trimethyltin on flavoraversion conditioning. Rats were first treated with either a dose of trimethyltin or a vehicle.…”

“…Flavor-aversion conditioning was arranged using lithium chloride after trimethyltin administration at a time when damage to the hippocampus was maximal (55). Unlike many previous studies, Peele et al (54) systematically varied the time between saccharin consumption and lithium chloride administration. Under these conditions lithium produced an aversion in control rats, the magnitude of which was an inverse function of the delay separating saccharin and lithium.…”