title: Long-term cognitive, emotional and neurogenic alterations induced by alcohol and methamphetamine exposure in adolescent rats.
abstract: A high proportion of young methamphetamine (MA) users simultaneously consume alcohol. However, the potential neurological and behavioural alterations induced by such a drug combination have not been systematically examined. We studied in adolescent rats the long-term effects of alcohol, MA, and alcohol and MA combined on anxiety-like behaviour, memory, and neurogenesis in the adult hippocampus. Rats received saline, ethanol (ETOH, 1.5g/kg), MA (MA, 2mg/kg), or ethanol and MA combined (ETHOH-MA, 1.5g/kg ethanol plus 2mg/kg MA) via oral gavage, once daily for 5 consecutive days. Open field (OF), elevated plus maze (EPM) and radial arm maze (RAM) tests were conducted following a 15-day withdrawal period. The results showed alterations in exploratory behaviour in the OF in the MA and ETOH-MA groups, and anxiety-like effects in the EPM in all three drug treatment groups. All three drug groups exhibited reference memory deficits in the RAM, but only the combination treatment group displayed alterations in working memory. Both MA and ETOH-MA treatments increased the length of doublecortin (DCX)-void gaps in the dentate gyrus but only ETOH-MA treatment increased the number of such gaps. An increased number and length of DCX-void gaps correlated with decreased exploratory activity in the OF, and impaired working memory in the RAM was associated with an augmented number of gaps. These findings suggest that alterations in adult hippocampal neurogenesis are linked to the persistent cognitive and behavioural deficits produced by alcohol and MA exposure.
authors.affiliation: Department of Psychology, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
authors.forename: David
authors.initials: D
authors.lastname: Loxton
authors.affiliation: Department of Neuroscience, Psychology and Behaviour, Medical Science Building, University of Leicester, University Road, Leicester LE1 9HN, United Kingdom. Electronic address: jjc30@leicester.ac.uk.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Canales
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003072:Cognition Disorders / Q000139:chemically induced*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004338:Drug Combinations; D000431:Ethanol / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008694:Methamphetamine / Q000633:toxicity*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018709:Statistics, Nonparametric; D013995:Time
chemical_list: D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004338:Drug Combinations; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D000431:Ethanol; D008694:Methamphetamine
keywords: Adult hippocampal neurogenesis; Alcohol; Anxiety; Memory; Methamphetamine