First, by receptor autoradiography and in situ hybridization (ISH) we have determined the neuronal localization of δ-9-tetrahydrocannabinol (THC) receptor and its mRNA in the adult brain of the rat and human as well as during development and aging. High concentrations were observed in the cerebral cortex, basal ganglia, hippocampus, hypothalamus and cerebellum in accordance with the clinical effects of cannabis use. In the basal ganglia, THC receptor mRNA were exclusively found in the striato-nigral and -pallidal neurons. Secondly, in the rat caudate-putamen (C-P), by ISH, those mRNA levels were increased after adrenalectomy, and were recovered following the addition of dexamethasone. They were also increased after 6-hydroxydopamine lesion and pharmacological blockade of dopamine receptors by antagonists SCH-23,390 (D1), haloperidol (D1&2) and sulpiride (D2), while they were decreased after aspiration cortectomy and MK801 treatment (glutamate antagonist of the NMDA type). Thus, in the C-P, there is a plasticity of THC receptor synthesis: down-regulation by glucocorticoids and dopamine and up-regulation by glutamate. Thirdly, in the rat C-P, by ISH, THC increased mRNA levels of the neuropeptides substance P and enkephalin. Thus, THC is a novel modulator of gene expression in the striatum. Together, these data suggest that THC and its endogenous cannabinoid play key functions in cognitive and motor regions of the brain.

PMID:

 

24105191

 

[PubMed – as supplied by publisher]