Dopamine synapse, pharmacology

Reid, R.T., Lloyd, G.K., and Rao, T.S., Pharmacological characterization of nicotine-induced acetylcholine release in the rat hippocampus in vivo evidence for a permissive dopamine synapse, Br. J. Pharmacol., 127, 1486, 1999. 

Dewey SL, Brodie JD, Gerasimov M, Horan B, Gardner EL, Ashby CRJ (1999) A pharmacologic strategy for the treatment of nicotine addiction. Synapse 31 76-86 Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats, Proc Natl Acad Sci USA 85 5274-5278... 

Cocaine is a local anesthetic with a peripheral sympathomimetic action that results from inhibition of transmitter reuptake at noradrenergic synapses (see Chapter 6 Introduction to Autonomic Pharmacology). It readily enters the central nervous system and produces an amphetamine-like effect that is shorter lasting and more intense. The major action of cocaine in the central nervous system is to inhibit dopamine reuptake into neurons in the "pleasure centers" of the brain. These properties and the fact that it can be smoked, "snorted" into the nose, or injected for rapid onset of... 

Levant B, Desouza EB (1993) Differential pharmacological profile of striatal and cerebellar dopamine receptors labeled by [3H]quinpirole. Identification of a discrete population of putative D3 receptors. Synapse 74 90-95. 

It was initially believed that the antidepressant effectiveness of MAOIs was the direct result of MAO inhibition. This acute effect decreases degradation of monoamines (e.g., norepinephrine, serotonin, or dopamine) stored in presynaptic neurons, thereby resulting in an increased amount of these neurotransmitters available at the synapse. More recent research indicates that this model does not fully explain the mechanism of MAOIs efficacy. For example, the positive (h-) stereoisomer of tranylcypromine is a poor antidepressant despite inhibiting MAO. The main pharmacologic difference between the negative (-) and + isomers of tranylcypromine is that the former has much weaker effects as a norepinephrine reuptake inhibitor in relation to its potency as an MAOI. The other MAOIs may also block the reuptake of selected neurotransmitters. However, like the non-MAOI uptake inhibitors, these acute effects often precede clinical antidepressant effects by weeks. More consistent with the 2- to 4-week lag in therapeutic effect, chronic treatment with a diverse number of MAOIs has been shown to reduce the number of a2- and P-adrenergic and serotonin (5-HT2) postsynaptic binding sites in the brain. 

Garris PA, Wightman RM (1995) Distinct pharmacological regulation of evoked dopamine efflux in the amygdala and striatum of the rat in vivo. Synapse 20 269-279. 

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