Cannabidiol, a non-psychoactive constituent of cannabis, has been reported as a neuroprotectant. Cannabidiol and Delta(9)-tetrahydrocannabinol, the primary psychoactive constituent of cannabis, significantly decreased the infarct volume at 4 h in the mouse middle cerebral artery occlusion model. The neuroprotective effects of Delta(9)-tetrahydrocannabinol but not cannabidiol were inhibited by SR141716, a cannabinoid CB1 receptor antagonist, and were abolished by warming of the animals to the levels observed in the controls. Delta(9)-Tetrahydrocannabinol significantly decreased the rectal temperature, and the hypothermic effect was inhibited by SR141716. These results surely show that the neuroprotective effect of Delta(9)-tetrahydrocannabinol are via a CB1 receptor and temperature-dependent mechanisms whereas the neuroprotective effects of cannabidiol are independent of CB1 blockade and of hypothermia.

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Abstract. The improving effects of various components of Toki-Shakuyaku-San (TSS) and fractions isolated from Angelica acutiloba Radix (Toki) on scopolamine-induced spatial memory impairment were investigated in eight-armed radial maze. The scopolamine-induced memory impairment was characterized by prominent increase of error choices in addition to decreased correct choices. Toki, Cnidium officinale Rhizoma (Senkyu), Poria cocos Hoelen (Bukuryo), Alisma orientale Rhizoma (Takusha), and Atractylodes lancea Rhizoma (Sojutsu) increased the correct choices, while only the Toki, Sojutsu, and Takusha decreased the error choices. No effect was produced by Paeonia lactiflora Radix (Shakuyaku). Investigation of effects of fractions isolated from Toki revealed that its activity mainly resided in the butanol layer and its contents of N-methyl-b-carboline-3-carboxamide and amines. Moreover, the alkaloid, internal and external solutions (containing poly-, di-, and monosaccharides) obtained by dialysis with Visking cellophane tubing also improved the memory. However, no improving properties were detected for methanol and hexanol layers, L-(-)-tryptophan, L-arginine, L-(-)-lysine, and choline chloride. The results showed that the TSS components could improve the reference and working memory impaired by scopolamine. The improving effect of TSS is produced greatly by the Toki component, the activity of which was greatly produced by the fraction extracted by butanol.

We studied the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), a 5-HT1A receptor agonist, on both delta9-tetrahydrocannabinol-induced spatial memory impairment in an 8-arm radial maze, and the reduction of acetylcholine release in the dorsal hippocampus as assessed by in vivo microdialysis in rats. A 6 mg/kg i.p. dose of delta9-tetrahydrocannabinol impaired spatial memory in the 8-arm radial maze and decreased the acetylcholine release in the dorsal hippocampus. 8-OHDPAT, at very low doses of 0.1-0.3 microg/kg, reversed both the impairment of spatial memory and the decrease in acetylcholine release induced by delta9-tetrahydrocannabinol. These findings suggest that low doses of 8-OHDPAT may improve delta9-tetrahydrocannabinol-induced impairment of spatial memory by enhancing acetylcholine release in the dorsal hippocampus.

In this study, the effect of ovariectomy and amyloid Beta(1-42) (ABeta(1-42))on eight-armed radial maze performance, acetylcholine (ACh) release, Alpha7nACh receptor (Alpha7nAChr), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression, and apoptosis of CA1 neurons in the dorsal hippocampus were investigated in rat. The results showed that the dorsal hippocampus of sham rats contains 136.7 -/+ 16.7 to 160.4 -/+ 21.1 fmol/microl ACh, and respective 201 -/+ 22.9 and 416.6 -/+ 66.3 expression of mRNA for a7nAChR and GAPDH. Ovariectomy alone, after 4 weeks, did not impair memory, and neither induced apoptosis nor changed the basal ACh release. On the other hand, ABeta(1-42) (600 pmol/10 microl/body/day i.c.v. for 7 days) impaired memory, an effect characterized by increased error choices and reduced (50-59%) ACh release, but only with slight apoptosis. Moreover, ovariectomy combined with ABeta(1-42) induced memory impairment characterized by decreased numbers of correct choices and increased numbers of errors. This effect was accompanied by a decrease of the basal ACh level (67%), a7nAChR mRNA expression (52%) and a7nAChR/GAPDH ratio (44%) without induction of apoptosis in the dorsal hippocampus. The high K+-evoked ACh release was not altered in ovariectomized rats, but was decreased by ABeta(1-42) (43%) and ovariectomy + ABeta(1-42) (80%). These results suggest that ovariectomy-induced hormonal deprivation after 4 weeks, when accompanied by ABeta(1-42) accumulation in the dorsal hippocampus, could impair memory by decreasing ACh release and a7nAChR expression without inducing apoptosis in the CA1 field of the dorsal hippocampus.