Serotonin, cannabinoid effects with

They found that a strain of mice that lacks the gene for NPY—NPY knockout mice—consume more ethanol than control mice and are less sensitive to ethanol s sedative effects. As would be expected if increased concentrations of NPY in the brain make mice more sensitive to ethanol, a strain of mice that overexpresses NPY drinks less alcohol than the controls even though their total consumption of food and liquid is normal. Work with other transgenic knockout mice support the central role in ethanol responses of signaling molecules that have long been believed to be involved (eg, GABA A, glutamate, dopamine, opioid, and serotonin receptors) and has helped build the case for newer candidates such as NPY and cannabinoid receptors, ion channels, and protein kinase C. 

Fig. 4 Effect of various peptides and nonpeptides on the electrically (3 Hz) evoked tritium overflow from superfused mouse brain cortex slices preincubated with 3H-serotonin. The evoked overflow represents quasi-physiological exocytotic serotonin release. In all experiments, serotonin autoreceptors were blocked by metitepine. The figure shows that human neuropeptide Y concentration-dependently inhibited serotonin release and that this effect was mimicked by human neuropeptide Y (13-36) (NPYi3 36), which has a high affinity for Y2 but a very low affinity for Yi receptors. These results are compatible with the view that neuropeptide Y acts via Y2 receptors in the present model. For the sake of comparison, the figure also shows the inhibitory effects of another three agonists, acting via cannabinoid CBi, histamine H3 and prostaglandin EP3 receptors and used at concentrations causing the maximum or near-maximum effect at their respective receptors. Drug concentrations in pM. P < 0.05, P < 0.003, compared to the control (from Nakazi et al. 2000 and Nakazi 2001 redrawn).

A synopsis of the inhibitory effects of cannabinoids on the release of the monoamines noradrenaline, dopamine and serotonin and of acetylcholine in the brain and the retina is given in Table 3. Noradrenaline release is inhibited via CBi receptors in the hippocampus of guinea-pig and man but not in the hippocampus of rat and mouse (Table 3, Fig. 4 Van Vliet et al. 2000). Although CBi receptors inhibit the release of dopamine from amacrine cells of the retina, contradictory results were obtained with respect to the modulation of dopamine release from... 

In addition to the effects of cannabinoids on the serotonergic metabolism, cannabinoids may affect the function of 5-HT receptors. The receptors for serotonin inclnde seven distinct classes (5-HTi to 5-HT7), with mnltiple members in each class (Hoyer et al., 2002). Although most of these receptors are G protein-coupled, the 5-HT3 receptor is the only ion channel receptor for serotonin in mammals (Derkach et al., 1989). Among the seven 5-HT receptors, only 5-HT2 and 5-HT3 receptors have to date been found to interact with cannabinoids. 

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