title: Amphetamine promotes task-dependent recovery following focal cortical ischaemic lesions in the rat.
abstract: This study investigated the effect of amphetamine (AMP) on skilled forelimb use following focal cortical ischaemic lesions in the rat. Unilateral lesions were produced by a novel method of intracortical microinjection of endothelin-1 (ET-1), intended to principally target the forelimb representation zone in primary motor-primary somatosensory cortex. Lesions were placed in the hemisphere contralateral to the preferred limb and produced deficits in skilled forelimb use on two tasks: the paw reach (PR) test and the foot fault (FF) test. Beginning on post-lesion day (D) 2, animals received injections of 2 mg/kg AMP and were injected every third day until D26. Animals were tested both during, and 24 h after, AMP administration. AMP facilitated recovery of skilled forelimb use on the PR test when assessed during drug-free test sessions. No such effect was seen on the FF test. These results demonstrate that sub-acute administration of AMP following a unilateral focal ischaemic lesion of FL can facilitate task-dependent recovery of skilled forelimb use in the rat. They also demonstrate that different behavioural tasks measuring superficially similar behavioural outputs may show different sensitivities to such drug effects.
authors.affiliation: Eli Lilly and Co. Ltd., Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, UK. gimour_gary@lilly.com
authors.forename: Gary
authors.initials: G
authors.lastname: Gilmour
authors.forename: Susan D
authors.initials: SD
authors.lastname: Iversen
authors.forename: Michael F
authors.initials: MF
authors.lastname: O'Neill
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Neill
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ward
authors.forename: David M
authors.initials: DM
authors.lastname: Bannerman
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology / Q000534:rehabilitation; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000534:rehabilitation; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019332:Endothelin-1; D005552:Forelimb; D007839:Functional Laterality; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000473:pathology; D009048:Motor Skills / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D020127:Recovery of Function / Q000187:drug effects*; D020521:Stroke / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D000071939:Stroke Rehabilitation
chemical_list: D000697:Central Nervous System Stimulants; D019332:Endothelin-1; D000661:Amphetamine