Treatment with Oxiracetam or Choline Restores Cholinergic Biochemical and Pharmacological Activities in Striata of Decorticated Rats

Abstract

Interruption of the corticostriatal pathway by undercutting the frontal cortex resulted after 2 weeks in a 40% reduction of basal acetylcholine (ACh) release in vivo, and in inhibition of the striatal sodium-dependent high-affinity uptake of choline (SDHACU) to the same extent. The lesion, too, completely prevented the rise (about 35%) in striatal ACh content induced by oxotremorine and apomorphine acting at muscarine and dopamine receptors, respectively. Acute intraperitoneal injections of 100 mg/kg of either oxiracetam or choline chloride resulted in time-dependent recovery of ACh output from the striata of decorticated rats to control levels. Oxiracetam also normalized the ex vivo striatal SDHACU activity of decorticated rats 2 h after administration without any effect in sham-operated rats. Oxiracetam or choline chloride administered before oxotremorine (0.8 mg/kg, i.p.) or apomorphine (1 mg/kg, i.p.) reinstated the ACh-increasing effect of these agonists. It is suggested that choline chloride acts directly simply by being the precursor for ACh, whereas oxiracetam may act indirectly, possibly by increasing the availability of choline chloride for ACh synthesis. Furthermore, the frontally decorticated rat could constitute a useful model for studying means to restore the deficit in striatal cholinergic neurotransmission.

Oxiracetam and aniracetam increase acetylcholine release from the rat hippocampus in vivo

“…In rats treated with oxiracetam this new steady-state is significantly higher than in controls. The hypothesis that oxiracetam may increase the availability of choline for ACh synthesis, suggested by Consolo et al [1990], based on indirect evidence, is therefore supported by the present findings indicating that the effective dose of oxiracetam in increasing the release of 4Ch from the hippocampus also increased choline levels in the effluent from the microdialysis tubing. On the other hand, an increase in phosphatidylcholine and phosphatidylethanolamine synthesis has been reported in aging rats treated repeatedly with oxiracetam [Trovarelli et al, 19861.…”

Trans‐synaptic Modulation of Striatal ACh Release In Vivo by the Parafascicular Thalamic Nucleus

“…2). Acute removal of excitatory corticostriatal afferents reduced ACh release by 40%, like chronic deafferentation (Consolo et al, 1990), thus supporting the notion that striatal cholinergic neurons are under the excitatory influence of the cortex.…”