Relapse to methamphetamine (Meth) use is often precipitated by exposure to drug-associated cues. Clinical studies suggest that cue-induced drug craving increases during early abstinence and remains elevated for extended time periods. An analogous phenomenon, termed 'incubation of drug craving' has been observed in rats trained to self-administer Meth. From an animal model-to-human translational perspective a limitation of rodent incubation studies is that the abstinence period preceding the relapse tests is experimenter-imposed (forced). In contrast, in humans, abstinence is often voluntary due the availability of alternative non-drug rewards. Based on these considerations, Dr. Caprioli recently developed a choice-based rat model of relapse after voluntary abstinence (1). The proposed model mimics human relapse after cessation of successful contingency management (CM) where the availability of monetary vouchers, given in exchange for 'clean' urine samples, maintains abstinence.
Notably, a recent clinical study, on the effectiveness of varying duration of a CM intervention in Meth addict, revealed that the number of participants who remained abstinence in a follow-up study increased as the exposure to CM increase.
Based on the above, the major objective of this proposal is to study over time similarity and differences of the synaptic alterations between the incubated Meth craving after forced and voluntary abstinence in rats. The central hypothesis, is that: both incubation after forced and voluntary abstinence-related plasticity in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) begins with decreased mGluR1 function enabling changes in AMPARs transmission, which promote Meth craving. However, a prolonged CM-based voluntary abstinence result in an attenuated cue-induced Meth seeking (as suggested by the human findings) and CP-AMPAR relative to the forced abstinence group.
