Frontal Decortication and Adaptive Changes in Striatal Cholinergic Neurons: Neuropharmacological and Behavioral Implications
Abstract
In neuropharmacological studies it was found that interruption of the corticostriatal pathway by undercutting the frontal cortex resulted after 2 weeks in marked reductions of basal ACh release in vivo determined by brain microdialysis and inhibition of the striatal sodium-dependent high-affinity uptake of choline (SDHACU). The lesion, too, completely prevented the rise in striatal ACh content induced by oxotremorine (OTMN) and r-apomorphine (APO). Acute i.p. injections of 100 mg/kg of either oxiracetam (OXI) or choline (Ch) resulted in time-dependent recovery of ACh output from the striata of decorticated (DC) rats to control levels. OXI also normalized the ex vivo striatal SDHACU activity of DC rats 2h after acute administration without exerting any effect in sham-operated rats. OXI or Ch administered before OTMN or APO reinstated the ACh-increasing effect of these agonists. In molecular mechanisms studies it was found that cortical deafferentation: 1), did not affect membrane fluidity and lipid phase transition of striatal synaptosomes and 2), produced a net reduction of 3H-Hemicholinium binding sites as ascertained by saturation and autoradiographic studies. In behavioral studies a general pattern of disinhibition was observed after lesion, reflected in a lack of stressful reactions in the presence of a novel object and low running times in the Lashley maze together with a marked deficit in active avoidance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 24, 1989
- Accession Number
- ADA217623
Entities
People
- Silvana Consolo
Organizations
- Mario Negri Institute for Pharmacological Research