If a physiological, biochemical or anatomical variable has a normal distribution then the tails of such a distribution may be associated with pathological function. In certain cases this can lead to a bimodal distribution for the variable in individuals with the resultant pathology. We illustrate with a study of dopamine receptors. PET data suggest that the distribution of dopamine DA2 receptor...

Prolactin release is a side effect of antipsychotic therapy with dopamine antagonists, observed in rats as well as humans. We examined whether two semimechanistic models could describe prolactin response in rats and subsequently be translated to predict pituitary dopamine D2 receptor occupancy and plasma prolactin concentrations in humans following administration of paliperidone or remoxipride....

How autoreceptors contribute to maintaining a stable output of rhythmically active neuronal circuits is poorly understood. Here, we examine this issue in a dopamine population, spontaneously oscillating hypothalamic rat (TIDA) neurons, that underlie neuroendocrine control of reproduction and neuroleptic side effects. Activation of dopamine receptors of the type 2 family (D2Rs) at the cell-body ...

The role of dopamine in behaviour and decision-making is often cast in terms of reinforcement learning and optimal decision theory. Here, we present an alternative view that frames the physiology of dopamine in terms of Bayes-optimal behaviour. In this account, dopamine controls the precision or salience of (external or internal) cues that engender action. In other words, dopamine balances bott...

Receptors that couple to phosphoinositide hydrolysis, which include metabotropic glutamate receptors (mGluRs) and muscarinic receptors, are known to either activate or inhibit the activity of dopamine cells depending on the pattern of receptor activation. Transient activation of alpha1 adrenoceptors with norepinephrine (NE) resulted in an outward current in midbrain dopamine neurons recorded in...

Anxiety-related behaviors increase histamine and dopamine release in the brain. On the other hand, central histamine counteracts reward and reinforcement processes mediated by the mesolimbic dopamine system. We investigated the effects of the histaminergic system and dopamine D2 receptors agents and their interactions on anxiety-related behaviors using the elevated plus-maze (EPM). The intra-hi...

We investigated whether semidehydroascorbic acid was an intermediate in norepinephrine synthesis in chromaffin granules and in electron transfer across the chromaffin granule membrane. Semidehydroascorbic acid was measured in intact granules by electron spin resonance. In the presence of intragranular but not extragranular ascorbic acid, semidehydroascorbic acid was formed within granules in di...

The best support for the hypothesized involvement of central nervous system dopamine systems in the pathophysiology of schizophrenia is the association between the affinity of neuroleptic drugs for the D2 dopamine receptor and their potency as antipsychotics. Discrepancy between the time course of receptor binding and the development of antipsychotic effects, however, limits this model. Preclin...

Postsynaptic Neuron Figure 1. Conventional vs. Atypical Antipsychotic Mechanisms n last month’s BRAINSTORMS, we discussed a new hypothesis on the mechanism of action of atypical antipsychotics, namely the “hit-and-run” hypothesis. Here we illustrate this concept. Conventional: Because of the biochemical properties of conventional antipsychotics, their binding to postsynaptic dopamine D2 recepto...

Typical antipsychotics have a high affinity for dopamine receptors. It is therefore of interest to investigate such loci in pharmacogenetic studies on psychosis. We investigated the hypothesis that Ser9Gly polymorphism of the DRD3 gene may play a role in the differences in individual response to typical antipsychotics between schizophrenic patients. The sample was composed of 53 good responders...