Dopamine

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Dopamine hypothesis of schizophrenia

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Originally proposed by van Rossum (1966) on the basis that antipsychotic drugs block dopamine receptors: schizophrenia results from excess dopaminergic activity, particularly in the mesolimbic system. The revised hypothesis (Davis et al., 1991) specifies a dual deficit — hyperdopaminergia in the mesolimbic pathway producing positive symptoms, and hypodopaminergia in the mesocortical pathway producing negative and cognitive symptoms. Further refinement followed evidence that atypical antipsychotics block D2 receptors only transiently and also antagonise serotonin 5-HT2A receptors, suggesting the full picture is more complex than simple D2 excess.

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Dopamine hypothesis of schizophrenia
Originally proposed by van Rossum (1966) on the basis that antipsychotic drugs block dopamine receptors: schizophrenia results from excess dopaminergic activity, particularly in the mesolimbic system. The revised hypothesis (Davis et al., 1991) specifies a dual deficit — hyperdopaminergia in the mesolimbic pathway producing positive symptoms, and hypodopaminergia in the mesocortical pathway producing negative and cognitive symptoms. Further refinement followed evidence that atypical antipsychotics block D2 receptors only transiently and also antagonise serotonin 5-HT2A receptors, suggesting the full picture is more complex than simple D2 excess.
Incentive salience ("wanting" vs "liking")
Berridge and Robinson's (1998) distinction between the motivational component of reward (wanting — the drive to pursue a reward, mediated by dopamine) and its hedonic component (liking — the pleasure experienced when obtaining it, mediated by opioid systems in the nucleus accumbens). In addiction, repeated drug exposure sensitises the wanting system while tolerance develops to the liking component, explaining why people compulsively seek drugs that no longer produce pleasure — one of the clearest demonstrations that motivation and hedonic experience are neurochemically separable.
D1 and D2 receptor families
Dopamine receptors are divided into two major families based on their signalling properties. D1-like receptors (D1, D5) couple to Gs proteins, activating adenylyl cyclase and increasing cAMP — they are the primary receptors in the mesocortical pathway mediating working memory and executive function. D2-like receptors (D2, D3, D4) couple to Gi proteins, inhibiting adenylyl cyclase — they are concentrated in the striatum and nucleus accumbens and are the primary targets of antipsychotic drugs. Understanding receptor subtype distribution explains the profile of both therapeutic effects and side effects of dopaminergic drugs.