Loss of resistance to punishment of cocaine use after prior experience

Audrey Durand, Paul Girardeau, Luana Freese, Serge H. Ahmed
Preprint bioRxiv. 2020-07-26; :
DOI: 10.1101/2020.07.24.219170

One behavioral feature of drug addiction is continued drug use despite awareness that this causes negative consequences. Attempts to model this feature in animals typically involve punishing drug self-administration with a brief electrical footshock and look for resistance to punishment. Though all individual animals eventually stop self-administering the drug with increasing intensity of punishment, some individuals do so at higher intensities than other individuals. The greater relative resistance to punishment of the former individuals is generally interpreted as evidence for a compulsion-like behavior. Here we show that resistance to footshock punishment is in fact not a stable individual behavioral feature. Specifically, when rats are retested for their resistance to increasing intensity of footshock punishment, they become much less resistant. As a result, they suppress their cocaine intake even when punished with an initially low and ineffective intensity. A series of original behavioral experiments reveals that this low resistance to footshock punishment is rapidly acquired after rats experience a punishment intensity that leads them to near-completely suppress their cocaine intake. Passive exposure to the same intensity does not induce this effect. Once acquired, low resistance to punishment persists during at least one month, but can nevertheless be extinguished by retesting rats on a daily basis. Interestingly, this acquired low resistance to footshock punishment does not generalize to a non-painful form of punishment (i.e., histamine) that is also seldom used in animal drug self-administration studies. We discuss some possible theoretical and methodological implications of these findings for future research on animal models of compulsion-like behavior.

Auteurs Bordeaux Neurocampus