Genetic differences in hippocampal synaptic plasticity

Synaptic plasticity is considered a physiological substrate for learning and memory Lynch MA (2004) Long-term potentiation and memory. Physiol Rev 84:87–136] that contributes to maladaptive learning in drug addiction Schoenbaum G, Roesch MR, Stalnaker TA (2006) Orbitofrontal cortex, decision-making and drug addiction. Trends Neurosci 29:116–124]. Many studies have revealed that drug addiction has a strong hereditary component Kosten TA, Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35–69; Uhl GR (2004) Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process. Neuropharmacology 47 (Suppl 1):140–147], however the contribution of the genetic background to drug-induced changes in synaptic plasticity has been scarcely studied. The present study reports on an analysis of long-term potentiation (LTP) and depotentiation in Lewis (LEW) and Fischer-344 (F344) rats, two inbred rat strains that show different proneness to drugs of abuse and are considered an experimental model of genetic vulnerability to addiction Kosten TA, Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35–69]. The induction of saturated-LTP was similar in LEW and F344 rats treated with saline or cocaine. However, only slices from LEW saline-treated rats showed the reversal of LTP; thus, the depotentiation of saturated-LTP was not observed in cocaine-injected LEW rats and in F344 animals (treated either with cocaine or saline). These results suggest significant differences in hippocampal synaptic plasticity between Lewis and Fischer 344 rats.