Dopamine, depression and antidepressants

Abstract

The relationship between depression and dopamine deficiency in the mesolimbic pathway has been hypothesized for many years. The experimental studies with animal models of depression and the human studies implicate the role of the dopamine system in depression. Not only do dopaminergic receptor agonists, but also antagonists such as olanzapine exhibit antidepressant effects associated with standard antidepressants in patients with treatment-resistant depression. This paradoxical result suggests that further investigations are necessary to understand the role played by dopamine in depression.

Discriminating Depression, Physical and Social Anhedonia by Neurotransmitter Related Challenge Tests

“…The results obtained for Global Depression confirm previous findings that low DA responses are characteristic of depressed patients (Pitchot et al, 1992;Hansenne et al, 2002;Dailly et al, 2004), but beyond this, the combined effect of low and late responses also emphasises the finding published by Depue et al (1994) that the time of the prolactin response to a bromocriptine challenge test may be as essential as its size. While a low size of response could be due to low production of DA, the late decrease of prolactin could also be due to pharmacokinetic factors in the periphery, like absorption and metabolism, but late or early responding to noradrenergic or serotonergic stimulation did not match the early versus late dopaminergic responses in our sample, so that kinetic causes in the periphery are unlikely.…”

“…Depressed patients also have been shown to exhibit low dopaminergic activity (Boadie et al, 2007) indicated e.g. by abnormal responses to dopamine agonists like apomorphine (Pitchot et al, 1992;Dailly et al, 2004;Stein, 2008).…”

Tonic Dopaminergic Stimulation Impairs Associative Learning in Healthy Subjects

“…Selectively for the PERGOLIDE group, subjects with greater (albeit not clinically relevant) baseline depression scores showed the least learning impairment under pergolide. The precise role played by dopamine in depression is not yet understood, but a deficient dopaminergic transmission seems to be one of the factors contributing to the symptoms of anhedonia (Dailly et al, 2004). With respect to our results, this would imply that subjects with less depressive moodFand hence higher baseline dopamine transmission ratesFwere more adversely affected by the administration of a dopamineagonistic substance as compared to subjects with lower baseline dopamine transmission rates.…”

Association of the COMT val158met Variant with Antidepressant Treatment Response in Major Depression

“…Under this model, function has been suggested to be optimal within a narrow range of dopamine activity, with too little or too much dopamine having relatively deleterious effects (Mattay et al, 2003). Thus, both the 158met/met genotype increasing dopamine levels as well as the 158val/val genotype impairing dopamine availability might contribute to the risk of nonresponse to antidepressant treatment, which across different studies might be modulated by factors extrinsic to the COMT 158val/met locus such as a specific constellation of genetic risk factors within the dopaminergic system, differential environmental risk factors, or different subclinical characteristics related to reduced or increased dopamine tonus in the respective samples of patients with depression (for review see Dailly et al, 2004). This notion of dose-dependency in the dopaminergic tonus with respect to depressive symptoms can be further illustrated by a case report observing improved depressive symptomatology on augmentation of antidepressant medication with bromocriptine 2.5-5 mg/day, whereas an increased dose of bromocriptine 15 mg/day resulted in a deteriorated clinical status (Wada et al, 2001).…”