Amphetamine promotes recovery from sensory-motor integration deficit after thrombotic infarction of the primary somatosensory rat cortex.

Abstract

The present studies were undertaken to examine 1) whether (/-amphetamine sulfate administered to rats well after thrombotic infarction of the vibrissal cortical barrel-field within the primary somatosensory cortex affected the rate and completeness of behavioral recovery and 2) whether a dose-response relation exists between (/-amphetamine sulfate dose and recovery of function. In a learning task requiring sensory-motor integration, 41 rats were trained to perform a motor response in a T-maze consequent to the detection of a vibrissal deflection cue. Once training was complete, unilateral (ft=29) or sham (n = 12) infarction was produced by a noninvasive photochemical technique. After infarction, T-maze performance was assessed repeatedly in rats receiving 2 (n = 10) or4(n=10) mg/kg J-amphetamine sulfate or saline (/i=9) 24 hours prior to testing on days 4, 6, 9, and 11. The sham-operated control rats received (/-amphetamine sulfate (n-1) or no injections (n-5). All three infarcted groups displayed a reliable and sustained behavioral deficit in performance that was not present in the shamoperated control animals. Although the performance of each infarcted group improved over the testing sessions after the first injection, the amphetamine-treated groups improved at a faster rate than the saline-injected group. The results further demonstrated a dose-response effect, with the 4 mg/kg amphetamine group recovering to within preinfarction levels 6-8 days earlier than the 2 mg/kg amphetamine and saline-injected groups. Moreover, both amphetaminetreated groups recovered more completely than the saline-injected group. Quantification of the chronic infarct area revealed no differences among the amphetamine-treated and saline-injected groups. These data provide further evidence of the facilitatory effect of (/-amphetamine sulfate on recovery from brain injury and extend this effect to the enhancement of recovery subsequent to thrombotic infarction of the primary somatosensory cortex. (Stroke 1991^22:648-654) S ince the turn of this century, the remarkable capacity for the brain to recover from cerebral injury, such as stroke, has spurred interest in the use of animal models to study mechanisms of functional recovery and apply them in the clinical setting.1 In recent years, data from animal studies Received August 27, 1990; accepted January 29, 1991. and preliminary clinical findings indicate that some pharmacologic manipulations that alter neurotransmitter (e.g., acetylcholine, •y-amino butyric acid, serotonin, dopamine, and norepinephrine [NE]) function may markedly promote recovery of function following brain injury. 2 One promising agent, the catecholamine agonist amphetamine, has been consistently shown during the past 20 years to reinstate locomotor, righting, and other postural reflexes and enhance recovery from learning and memory deficits induced by electrolytic brain lesions. 2^1 In particular, one recent study found that a single dose of amphetamine given to cats 10 days after unilateral motor cortex ablation...

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.…”

“…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.…”

D-Amphetamine Boosts Language Learning Independent of its Cardiovascular and Motor Arousing Effects

“…The AMPH doses required to boost recovery affect mainly noradrenergic, dopaminergic, and, to a lesser extent, serotonergic neurotransmission (Hurwitz et al, 1991). The design of our study does not allow to directly disentangle noradrenergic from dopaminergic effects of AMPH.…”

Nogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity

“…It is likely that both anatomical changes in the pattern of existing connectivity and altered electrical patterns in stable connections account for these shifts in activation patterns during specific tasks. There is some evidence that plasticity and recovery after stroke can be enhanced in the subacute phase by focused training regimens (van der Lee et al, 1999;Bland et al, 2001;Liepert et al, 2001;Wolf et al, 2002) or by increased monoaminergic activation with D-amphetamine (Hurwitz et al, 1991;Walker-Batson et al, 1995;Stroemer et al, 1998;Knecht et al, 2001;Sonde et al, 2001;Walker-Batson et al, 2001). Inosine and FGF treatments have also been reported to increase axonal plasticity and functional recovery from stroke in rodents (Kawamata et al, 1997;Chen et al, 2002); however, there is currently no clinically useful pharmacological method to enhance stroke recovery.…”