Dopaminergic receptor sensitivity

The Dj-dopaminergic receptor decreases cAMP production by inhibiting dopamine-sensitive adenylyl cyclase and opens channels but can also block Ca++ channels. It is located both presynaptically and postsyn-aptically on neurons in the caudate putamen, nucleus accumbens, and olfactory tubercle. Another member of this family is the Dj-receptor, which also decreases... 

None of the TCAs seem to have an effect on dopaminergic neurotransmission in the central nervous system (CNS). This has been supported by the lack of alterations in dopamine receptor sensitivity in chronically treated patients who have shown response to treatment (Sugrue, 1983). More recent investigations have also shown that administration of DMI to depressed subjects had no effect on levels of homovanillic acid, the principal metabolite of dopamine, in a measure of brain neurotransmitter production. In this investigation, DMI administration did increase norepinephrine production and overall cerebral metabolism (Lambert, 2000). 

Schizophrenia appears to be caused by an overactivity of dopamine pathways in certain parts of the brain such as the limbic system.2,23 This idea is based primarily on the fact that most antipsychotics block dopamine receptors, thereby reducing dopaminergic hyperactivity in mesolimbic pathways and other limbic structures (see the next section of this chapter). The increased dopamine influence underlying psychosis could be caused by excessive dopamine synthesis and release by the presynaptic neuron, decreased dopamine breakdown at the synapse, increased postsy-naptic dopamine receptor sensitivity, or a combination of these and other factors. 

Antagonists of catecholaminergic function have also been used. The neuroleptics haloperidol (a centrally acting butyrophenone) and (- )sulpiride have been administered to lead-dosed animals. Lucchi etal. (1981) found that rats dosed with 2.5 g Pb/1 (1365 ppm Pb) showed no differences in halo-peridol-induced sedation, while the dose of (-)sulpiride which caused sedation was lower in lead-intoxicated animals than in control rats. These observations suggest that one of the neurochemical changes that may be ascribed to lead is an alteration in receptors sensitive to (-)sulpiride, i.e. a discrete population of dopaminergic D2 receptors. 

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