title: The long-term effects of methamphetamine exposure during pre-adolescence on depressive-like behaviour in a genetic animal model of depression.
abstract: Methamphetamine (METH) is a psychostimulant and drug of abuse, commonly used early in life, including in childhood and adolescence. Adverse effects include psychosis, anxiety and mood disorders, as well as increased risk of developing a mental disorder later in life. The current study investigated the long-term effects of chronic METH exposure during pre-adolescence in stress-sensitive Flinders Sensitive Line (FSL) rats (genetic model of depression) and control Flinders Resistant Line (FRL) rats. METH or vehicle control was administered twice daily from post-natal day 19 (PostND19) to PostND34, followed by behavioural testing at either PostND35 (early effects) or long-lasting after withdrawal at PostND60 (early adulthood). Animals were evaluated for depressive-like behaviour, locomotor activity, social interaction and object recognition memory. METH reduced depressive-like behaviour in both FSL and FRL rats at PostND35, but enhanced this behaviour at PostND60. METH also reduced locomotor activity on PostND35 in both FSL and FRL rats, but without effect at PostND60. Furthermore, METH significantly lowered social interaction behaviour (staying together) in both FRL and FSL rats at PostND35 and PostND60, whereas self-grooming time was significantly reduced only at PostND35. METH treatment enhanced exploration of the familiar vs. novel object in the novel object recognition test (nORT) in FSL and FRL rats on PostND35 and PostND60, indicative of reduced cognitive performance. Thus, early-life METH exposure induce social and cognitive deficits. Lastly, early-life exposure to METH may result in acute antidepressant-like effects immediately after chronic exposure, whereas long-term effects after withdrawal are depressogenic. Data also supports a role for genetic predisposition as with FSL rats.
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, Division of Pharmacology, North-West University, Internal box 16, Potchefstroom campus, Potchefstroom, 2520, Republic of South Africa.
authors.forename: Moné
authors.initials: M
authors.lastname: Mouton
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, Division of Pharmacology, North-West University, Internal box 16, Potchefstroom campus, Potchefstroom, 2520, Republic of South Africa.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Harvey
authors.affiliation: Research Entity for Medicine Usage in South Africa, Faculty of Health Sciences, North-West University, Potchefstroom, 2520, South Africa.
authors.forename: Marike
authors.initials: M
authors.lastname: Cockeran
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, Division of Pharmacology, North-West University, Internal box 16, Potchefstroom campus, Potchefstroom, 2520, Republic of South Africa. tiaan.brink@nwu.ac.za.
authors.forename: Christiaan B
authors.initials: CB
authors.lastname: Brink
mesh_terms: D019969:Amphetamine-Related Disorders / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D000697:Central Nervous System Stimulants; D003863:Depression / Q000235:genetics* / Q000523:psychology*; D005260:Female; D006120:Grooming; D007398:Interpersonal Relations; D008297:Male; D008694:Methamphetamine; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects; D013550:Swimming / Q000523:psychology
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine
keywords: Depression; Early-life exposure; Finders Sensitive Line; Flinders Resistant Line; Methamphetamine