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d-Amphetamine improves cognitive deficits and physical therapy promotes fine motor rehabilitation in a rat embolic stroke model


Rune Skovgaard Rasmussen, Neurovascular Research Laboratory, Dept. 5463, Copenhagen University Hospital, DK – 2100, Copenhagen, Denmark
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Background and Purpose –  The purpose of this study was to examine the effects of d-amphetamine (d-amph) and physical therapy separately or combined on fine motor performance, gross motor performance and cognition after middle cerebral artery thromboembolization in rats.

Methods –  Seventy-four rats were trained in appropriate cognitive and motor behaviours. Thirteen animals were sham-operated and fifty-nine animals were embolized in the right carotid territory. Animals were randomly assigned to five groups: 1) SHAM (non-embolized, saline), 2) CONTROL (embolized, saline), 3) D-AMPH (embolized, d-amph), 4) THERAPY (embolized, saline + physical therapy) and 5) D-AMPH + THERAPY (embolized, d-amph + physical therapy). Rats of the groups 4–5 underwent d-amph or saline treatment on days 1, 3, 5 and 7 after surgery and were re-trained for 1 h starting 60 min after each treatment. During this time, rats were allowed to voluntarily engage in suitable cognitive or motor behaviours in order to obtain food. Animals from all groups were re-tested during days 21–28 after surgery.

Results –  No differences in infarct volumes were observed between the groups of embolized animals. When evaluating performances on days 21–28 after surgery, rats of the SHAM and THERAPY groups had better fine motor performance than those of the CONTROL (P < 0.05), whereas rats of SHAM and D-AMPH groups achieved better cognitive performance than CONTROL rats (P < 0.05). No significant differences were observed between any groups regarding gross motor performance.

Conclusions –  After embolization, physical therapy improved fine motor performance and d-amph accelerated rehabilitation of cognitive performance as observed in the rats of the THERAPY and D-AMPH groups. As a result of the administration of a high dose of d-amph, the rats of the D-AMPH + THERAPY combination group failed to engage in physical therapy during d-amph intoxication, thereby limiting any promotion of rehabilitation by combining physical therapy and d-amph.