Amphetamine, Haloperidol, and Experience Interact to Affect Rate of Recovery After Motor Cortex Injury

Abstract

Rats subjected to unilateral ablation of the motor cortex and placed on a narrow beam displayed transient contralateral paresis. An immediate and enduring acceleration of recovery was produced by a single dose of d-amphetamine given 24 hours after injury. This effect was blocked by haloperidol or by restraining the animals for 8 hours beginning immediately after amphetamine administration. A single dose of haloperidol given 24 hours after injury markedly slowed recovery. This effect was also blocked by restraining the animals.

Amphetamine increases blood pressure and heart rate but has no effect on motor recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled trial (ISRCTN 36285333)

“…It is possible that higher and more frequent doses are required, as tested in experimental models. 5,9,47,48 Fourth, treatment was started between 4 and 30 days after stroke onset. Similar studies have failed to address the issue of most favourable time to recruitment and the optimal therapeutic window remains to be elucidated.…”

“…3,4 In experimental models cerebral ischaemia results in a catecholamine deficit, whereas drugs that negatively regulate central neurotransmitters, such as haloperidol, (a dopamine receptor antagonist), have detrimental affects on outcome in both experimental and clinical stroke. 5,6 It has been hypothesized that increasing catecholamines could facilitate recovery following stroke, and that centrally acting neurotransmitters might modulate plasticity. 7,8 Amphetamine, a sympathomimetic drug, has been shown to accelerate the recovery of motor function in experimental models of stroke when given in conjunction with task-specific practice.…”

“…7,8 Amphetamine, a sympathomimetic drug, has been shown to accelerate the recovery of motor function in experimental models of stroke when given in conjunction with task-specific practice. 5,9,10 However, timing and dose of administration appears important; high doses and early administration being associated with a poor outcome, 5,11 whereas pretreatment with amphetamine led to increased ischaemic insult. 12 The evidence in normal subjects [13][14][15] and in clinical stroke is less clear, [16][17][18][19][20][21][22][23][24][25][26][27] numerous small trials, utilising varying dosage and timing of treatment, showing conflicting results, overall demonstrating no evidence of benefit on motor recovery.…”

Gender associations with chronic methylphenidate treatment and behavioral performance following experimental traumatic brain injury

“…The beam-walking task was utilized to evaluate fine motor coordination and function using a paradigm [39] adapted from that first reported by Feeney et al [8]. Two days prior to surgery, animals were trained to escape a loud noise by traversing a narrow beam (2.7 cm width) and entering a darkened goal box.…”

Stroke, with or with no ice? Observations on amphetamine for the management of acute stroke

“…8,9 Relevant stroke studies on amphetamine did not become available until the early 1990s, the most cited ones being Goldstein's work on facilitated recovery of beam walking 10 and Ginsberg's research on vibrissae stimulation-induced elevation of glucose utilization in stroke rats treated with amphetamine. 11 Consistent across these laboratory studies is that D-amphetamine is shown to enhance recovery when the drug is paired with lesion-specific training or sensory stimulation, paving the way to introduce pharmacologic enhancement of recovery after focal brain injury as a justified treatment regimen for stroke patients undergoing physical therapy.…”