title: Enduring deficits in sustained visual attention during withdrawal of intravenous methylenedioxymethamphetamine self-administration in rats: results from a comparative study with d-amphetamine and methamphetamine.
abstract: Although amphetamine-derived stimulants are widely associated with neurotoxicity, it is poorly understood whether extended exposure to such drugs produces lasting effects on neurocognitive function. This study investigates whether chronically self-administered d-amphetamine, methamphetamine (MA), or methylenedioxymethamphetamine (MDMA) leads to residual deficits in a rodent test of sustained visual attention and impulsivity. Rats were trained on a five-choice serial reaction time task and subsequently trained to self-administer d-amphetamine, MA, or MDMA (all 50 microg/infusion), intravenously, for 3 weeks. Effects on performance were evaluated 24 h after drug discontinuation and for several weeks thereafter, including various challenge sessions to increase the attentional demands of the task. The results indicate divergent patterns of self-administration among the three drugs tested with increasing rates of intake evident in rats self-administering amphetamine, but not MA, and widely fluctuating rates in the MDMA group. Withdrawal of MA resulted in severe behavioral disturbances, with significant effects on accuracy, omissions, response latency, and impulsivity that lasted up to 2 weeks in some cases. Amphetamine and MDMA withdrawal were associated with similar, but shorter-lasting effects on performance. However, when challenged with a high event rate session 6 weeks after drug discontinuation, rats previously exposed to MDMA continued to show deficits in the accuracy and speed of responding. These findings show that amphetamine-derived stimulants have both short- and long-term consequences for psychomotor functioning. The demonstration of residual deficits in rats chronically exposed to MDMA raises some concern about the potential harm caused by this drug in human ecstasy users.
authors.affiliation: Department of Experimental Psychology and Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK. jwd20@cam.ac.uk
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Dalley
authors.forename: Kristjan
authors.initials: K
authors.lastname: Lääne
authors.forename: David E H
authors.initials: DE
authors.lastname: Theobald
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Peña
authors.forename: Charlotte C
authors.initials: CC
authors.lastname: Bruce
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Huszar
authors.forename: Michael
authors.initials: M
authors.lastname: Wojcieszek
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Everitt
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
mesh_terms: D019969:Amphetamine-Related Disorders / Q000503:physiopathology*; D000662:Amphetamines / Q000009:adverse effects*; D000818:Animals; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000009:adverse effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D003913:Dextroamphetamine / Q000009:adverse effects; D006213:Hallucinogens / Q000009:adverse effects; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D010468:Perceptual Disorders / Q000139:chemically induced / Q000503:physiopathology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013995:Time; D014796:Visual Perception / Q000187:drug effects
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D006213:Hallucinogens; D008694:Methamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003913:Dextroamphetamine