Cortex drug dependence

Cannon CM, Palmiter RD (2003) Reward without dopamine, J Neurosci 23 10827-10831 Carboni E, Bortone L, Giua C, Di Chiara G (2000) Dissociation of physical abstinence signs from changes in extracellular dopamine in the nucleus accumbens and in the prefrontal cortex of nicotine dependent rats. Drug Alcohol Depend 58 93-102 Castane A, Valjent E, Ledent C, Parmentier M, Maldonado R, Valverde O (2002) Lack of CBl cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence. Neuropharmacology 43 857-867... 

Experimental evaluation of the analgesic activity of a given drug in humans is difficult, for the reactivity to a painful stimulus varies in different individuals and even in the same individual from time to time. The analgesic action depends on the alteration of the transmission of the pain impulse from the periphery to the cerebral cortex but is modified by psychic factors. 

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).

With regard to its effect on neurotransmitter function, alcohol increases adenylate cyclase activity, possibly via the membrane-bound G protein complex. The effect of alcohol on the secondary messenger system appears to depend on its location the noradrenaline-linked cyclase in the cortex seems to be directly affected by the drug, whereas the dopamine-linked enzyme in the basal ganglia appears to be altered by a combination of changes in the membrane fluidity, together with those in the G protein-cyclase complex. 

As mentioned in Chapter 1, perhaps the purest form of drug therapy is the replacement of inadequate amounts of an endogenous substance such as a hormone. Any gland that normally secretes a hormone is a potential target for hypofunctioning. Classical examples include Addison s disease (adrenal cortex), dwarfism (anterior pituitary), juvenile-onset insulin-dependent diabetes (pancreas), and hypothyroidism (thyroid). 

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