Hippocampus specific receptors

The primary active component of cannabis is A9-tetrahy-drocannabinol (THC), which is responsible for the greater part of the pharmacological effects of the cannabis complex. A8-THC is also active. However, the cannabis plant contains more than 400 chemicals, of which some 60 are chemically related to A9-THC, and it is evident that the exact proportions in which these are present can vary considerably, depending on the way in which the material has been harvested and prepared. In man, A9-THC is rapidly converted to 11-hydroxy-A9-THC (5), a metabolite that is active in the central nervous system. A specific receptor for the cannabinols has been identified it is a member of the G-protein-linked family of receptors (6). The cannabinoid receptor is linked to the inhibitory G-protein, which is linked to adenyl cyclase in an inhibitory fashion (7). The cannabinoid receptor is found in highest concentrations in the basal ganglia, the hippocampus, and the cerebellum, with lower concentrations in the cerebral cortex. 

Gonzalez, A.-M., Lappi, D.A., Buscaglia, M.L., Carman, L.S., Gage, F.H. and Baird, A. (1991b) Basic FGF-SAP mito-toxin in the hippocampus specific lethal effect on cells expressing the basic FGF receptor. Ann. N. Y. Acad. Sci. 638 442-444. 

Low concentrations of solubilised jS-albumin inhibit ACh release in slices from rat hippocampus and cortex areas which show degeneration in AzD, but not in slices from the striatum which is unaffected. While not totally specific to ACh, since some inhibition of NA and DA and potentiation of glutamate release have been reported, this effect is achieved at concentrations of A/i below those generally neurotoxic. Since jS-amyloid can inhibit choline uptake it is also possible (see Auld, Kar and Quiron 1998) that in order to obtain sufficient choline for ACh synthesis and the continued function of cholinergic neurons, a breakdown of membrane phosphatidyl choline is required leading to cell death (so-called autocannibalism), /i-amyloid can also reduce the secondary effects of Mi receptor activation such as GTPase activity... 

NGF also has actions within the CNS, although it is not particularly abundant in the CNS. Its synthesis appears to be largely restricted to the hippocampus and neocortex, and even in these regions it is present at relatively low concentrations relative to the other neurotrophins. The most prominent population of NGF-responsive neurons expressing TrkA are the basal forebrain cholinergic neurons. The principal projections of these neurons are to the hippocampus and cortex, which conforms with the concept that NGF acts as a target-derived trophic factor in the CNS, just as it does in the peripheral nervous system (PNS). NGF also acts on a subpopulation of cholinergic neurons within the striatum. These interneurons express the NGF receptor, TrkA, and respond to NGF. However, they do not appear to rely entirely on NGF for their survival, and the specific actions of NGF on this neuronal population have not been clearly defined. NGF may also have autocrine actions in the CNS, as some neuronal populations have been identified that express both TrkA and NGF. 

Another problem in validating targets for behavioral disorders related to neurotransmitter abnormalities is the interplay between several neurotransmitter systems in specific brain regions. For example, in the hippocampus, limbic, and nigral-striatal areas, functions connected by serotonin, norepinephrine, and dopamine are interconnected so that blocking selected receptor subtypes or changing synaptic levels of certain neurotransmitters may... 

Chronic exposure to THC causes a regulation of cannabinoid receptors, which appears to be region-specific (Zhuang et al. 1998). For example, while increases in cannabinoid receptor mRNA are seen in the cerebellum and hippocampus at 7 and 14 days of chronic treatment, decreases were seen in the striatum from days 2 to 14. However, levels returned to normal in all the regions by day 21, which coincides with reports of behavioral tolerance. 

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