Drug memory substitution during re-consolidation: a single inhibitory autoreceptor apomorphine treatment given during psychostimulant memory re-consolidation replaces psychostimulant conditioning with conditioned inhibition and reverses psychostimulant sensitization.

Psychostimulant conditioning and sensitization effects have proven to be difficult to eliminate using behavioral methods. We used a low autoreceptor dose of apomorphine in counter-conditioning and memory re-consolidation protocols to modify conditioned and sensitized responses induced by a high dose of apomorphine. Rats received five daily treatments of apomorphine (2.0mg/kg) and were tested in an arena for 30 min to induce conditioning and sensitization. Conditioning was validated in a brief 5 min non-drug conditioning test and sensitization by a 2.0 apomorphine challenge test. Next, the counter-conditioning and memory re-consolidation protocols were initiated. In counter-conditioning, vehicle or 0.05 mg/kg apomorphine was given either 15 min or immediately before a 5 min arena test. In the memory re-consolidation protocol, the vehicle and 0.05 apomorphine treatments were administered post-trial either immediately after or 15 min after the 5 min arena test. Effects were assessed with a 5 min saline conditioning test and a second 2.0mg/kg apomorphine challenge test. The counter-conditioning protocol induced hypolocomotion and but did not induce a conditioned hypo-locomotion and did not alter the sensitized response. The 15 min post-trial treatment did not affect either the conditioned or the sensitized responses. The immediate post-trial treatment eliminated sensitization and induced a conditioned hypoactivity response. These results highlight the memory re-consolidation period as a critical target for drug memory substitution and suggest the potential utility of the pharmacological inhibition of dopamine activity given as a therapeutic drug memory replacement during addictive drug memory re-consolidation.