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Behavioural and neurochemical changes associated with single and combined acetylcholine and dopamine lesions in neonatal rats.

Sherren N, Pappas BA (2001) Behavioural and neurochemical changes associated with single and combined acetylcholine and dopamine lesions in neonatal rats. Neuroscience 2001 Abstracts 539.5. Society for Neuroscience, San Diego, CA.

Summary: The functional outcomes of neonatal ACh or DA lesions are frequently less severe or qualitatively different from those seen in adult rats, and may be due to compensatory neurochemical changes. Given that these transmitter systems interact in the adult brain and that ACh and DA hypofunction may underlie the cognitive and motor disabilities seen in Rett syndrome, we hypothesized that combined neonatal ACh/DA lesions may produce a profile of neurochemical changes and behavioural impairments which are more severe or distinct from that caused by either lesion alone. Rats were lesioned at postnatal day 7 with 192 IgG-saporin (ACh rats), 6-OHDA with NE receptor blockade (DA rats), or both (ACh/DA rats). Behavioural testing occurred at 4 months of age. In the open field, only ACh/DA rats exhibited locomotor hyperactivity whereas all lesioned groups exhibited reduced exploratory behaviour. Neither DA nor ACh/DA rats were able to solve the Morris water maze, however ACh rats were indistinguishable from controls. 192 IgG-saporin treatment produced a 75% decrease in hippocampal ChAT activity, and cortical decreases of 30%, 70% and 40% in the frontal/cingulate (FC), retrosplenial (RS) and partietotemporal (PT) regions respectively. 6-OHDA treatment produced a 90% decrease in striatal DA levels and a 75% decrease in FC cortex. Interestingly PT DA levels were 68% higher in ACh rats but 47% lower in ACh/DA rats compared to control, while DA rats showed a decrease which was not significantly different from control. Thus sparing of spatial learning ability in ACh rats may be mediated by increases in PT DA levels, whereas combined ACh/DA lesions exacerbate DA loss in this region.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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