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.
Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes 28013-602, RJ, Brazil.
João Marcos
JM
de Mello Bastos
Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes 28013-602, RJ, Brazil.
Flávia Regina Cruz
FR
Dias
Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes 28013-602, RJ, Brazil.
Victor Hugo Nicácio
VH
Alves
Research and Development (151), VA Medical Center, Central New York Research Corporation and SUNY Upstate Medical University, 800 Irving Avenue, Syracuse, NY 13210, USA.
Robert J
RJ
Carey
Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes 28013-602, RJ, Brazil. Electronic address: marinete@uenf.br.
Marinete Pinheiro
MP
Carrera
D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology*; D017660:Autoreceptors / Q000819:agonists; D003213:Conditioning, Psychological / Q000187:drug effects*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019966:Substance-Related Disorders / Q000188:drug therapy*
D017660:Autoreceptors; D018491:Dopamine Agonists; D001058:Apomorphine
Apomorphine; Conditioning; Counter-conditioning; Memory re-consolidation; Memory substitution; Sensitization