Strain differences between Lewis and Fischer 344 rats in the modulation of dopaminergic receptors after morphine self-administration and during extinction

Abstract

The Lewis (LEW) and Fischer 344 (F344) rat strains have been used as a model to study genetic vulnerability to drug addiction and they differ in their dopaminergic systems. We have studied the variation in the D1-like and D2-like receptors in distinct brain regions of LEW and F344 rats that self-administered morphine (1 mg/kg) for 15 days and also after different extinction periods (3, 7 and 15 days). Under basal conditions, binding to D1-like receptors in the olfactory tubercle and substantia nigra, and to D2-like receptors in the Pyriform cortex and hippocampal-CA1 was lower in LEW rats than in F344 rats. Conversely, the LEW rats exhibited stronger D2-like binding in the caudate-putamen. In most brain regions there was a decrease in D1-like binding in LEW rats after self-administration while the F344 animals displayed an increment. Additionally, D2 receptors of LEW rats were down-regulated after self-administration in the caudate-putamen and in the nucleus accumbens (shell and core divisions). Binding to D1-like receptors increased in both strains in the early phases of extinction, while in the later stages a differential regulation was observed between both strains. During the early phases of extinction only F344 rats showed alterations in D2-like receptor binding, however in the latter phases a specific modulation occurred in both strains. These differences in basal D1-like and D2-like receptor binding, and their differential modulation after self-administration and during extinction, may be reflected in the greater vulnerability to opiate addiction shown by LEW strain.