Behavioral Economics of Individual Differences in METH Preference

摘要

Background:The rat drug self-administration (SA) model is a classic and widely used paradigm for studying the neurobiological mechanisms of drug addiction.However,despite decades of research using this model,no breakthrough has been made in addiction treatment or prevention.Recent studies have begun to critically re-evaluate the validity of classifying all drug SA rats as addiction models,emphasizing instead the importance of individual variability and the need to assess distinct stages of addiction development.Therefore,establishing a behavioral paradigm that can accurately assess addiction severity in rats is both scientifically and clinically urgent.Objective:This study aimed to evaluate addiction severity in rats by measuring their preference for drug rewards versus natural rewards in a choice-based paradigm.We compared this approach with conventional methods for assessing drug-seeking behavior to develop a refined model for distinguishing addictionrelated traits.We also investigated the role of dopamine receptor signaling in mediating rewardpreference.Methods:After reliable acquisition of methamphetamine (METH) and saccharin (SACC)self-administration,rats underwent a choice experiment to classify individuals based on reward preference.Demand elasticity for METH was assessed using a within-session behavioral economics procedure.To examine the role of dopaminergic signaling,a low-dose dopamine receptor antagonist was administered intraperitoneally,and its effects on choice behavior were evaluated.Results:In the choice experiment,most METH self-administering rats (21/30) preferred SACC over METH.METH-preferring rats showed higher demand elasticity for METH (i.e.,lower essential value) compared to SACC-preferring rats.Demand elasticity for METH was positively correlated with METH choice rate.Pharmacological blockade of dopamine receptors increased METH demand elasticity and elevated METH selection in initially SACC-preferring rats,indicating a critical role of dopaminergic transmission in reward valuation.

关键词

self-administering / methamphetamine / choice / behavioral economics;dopamine