title: Evidence of memory generalization in contextual locomotor sensitization induced by amphetamine.
abstract: Addiction is a multifactorial disease that comprises physiological mechanisms of learning and memory. Addict subjects have intense plasticity in cortical and limbic circuits during intoxication, abstinence or even in drug seeking behavior. Locomotor sensitization is a classic animal model of drug addiction that mimics the changes that occur in the transition from drug use to drug addiction. Several studies have demonstrated the importance of contextual associative processes in this task. However, whether the mechanisms of sensitization are maintained and precise over the time remain an open question. Thus, the aim of this study was to investigate the importance of context in the maintenance and precision of locomotor sensitization across time. For this, male c57bl/6 mice were submitted to different contexts during the acquisition phase of amphetamine-induced locomotor sensitization. We found that after 3days of withdrawal, the expression of locomotor sensitization was context dependent, as characterized by an increased locomotion in the acquisition context (A), but not in the novel context (B). Surprisingly, when the expression of locomotor sensitization was tested after 28days of withdrawal, mice that acquired sensitization in the context A exhibited increased locomotion in both contexts (A and B), suggesting that memories associated with amphetamine drugs generalize following long periods of abstinence. The same generalization did not occur in mice sensitized in a well-known context (home cage). These results demonstrate, for the first time, the influence of memory generalization in amphetamine-induced locomotor sensitization. The evidence that memory generalization also occurs in sensitization provides new advances in the comprehension of the mechanisms underlying memory role in addiction process. Elucidating the mechanisms of amphetamine sensitization may shed some light on understanding the transition from drug use to addiction.
authors.affiliation: Laboratory of Neurobiology, Universidade Federal de Sao Paulo, Pedro de Toledo St, 669, 3° floor, Sao Paulo, SP 04039-032, Brazil. Electronic address: douglas.engelke@gmail.com.
authors.forename: Douglas Senna
authors.initials: DS
authors.lastname: Engelke
authors.affiliation: Laboratory of Neurobiology, Universidade Federal de Sao Paulo, Pedro de Toledo St, 669, 3° floor, Sao Paulo, SP 04039-032, Brazil.
authors.forename: Renato
authors.initials: R
authors.lastname: Filev
authors.affiliation: Laboratory of Neurobiology, Universidade Federal de Sao Paulo, Pedro de Toledo St, 669, 3° floor, Sao Paulo, SP 04039-032, Brazil.
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Mello
authors.affiliation: Laboratory of Neurobiology, Universidade Federal de Sao Paulo, Pedro de Toledo St, 669, 3° floor, Sao Paulo, SP 04039-032, Brazil; Department of Physiological Science, Faculdade de Ciências Médicas de São Paulo. R. Cesário Motta Jr, 61, 12° andar, São Paulo, SP 01221-020, Brazil.
authors.forename: Jair Guilherme
authors.initials: JG
authors.lastname: Santos-Junior
mesh_terms: D000661:Amphetamine / Q000009:adverse effects* / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004195:Disease Models, Animal; D005793:Generalization, Psychological / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D000661:Amphetamine
keywords: Addiction; Amphetamine; Behavioral sensitization; Contextual memory; Drugs; Psychostimulants