Dopaminergic signaling

The forced swim test and other assays that are used to identify antidepressant compounds detect compounds with different types of drug action—i.e., serotonin reuptake blockers, norepinephrine reuptake blockers, and atypical antidepressants. A major concern with these types of assays is the identification of false positive compounds. Traditionally, test compounds are evaluated in the forced swim test and in locomotor activity assays to test for stimulant activity. Stimulant compounds are considered false positives in the forced swim test since swimming is considered by some a form of locomotion. However, there are some compounds that increase dopaminergic signaling, such as nomifensine and bupropion, that had antidepressant-like effects in clinical and preclinical tests and demonstrated stimulant activity in some studies [37,38]. Interestingly, stimulant drugs are normally considered false positives in the forced swim test because they are not prescribed for depressed patients however, no controlled studies have been conducted to test this assumption. 

Kotter R. 1994. Postsynaptic integration of glutamatergic and dopaminergic signals in the striatum. Prog Neurobiol 44 163-196. 

Nishi A, Bibb JA, Snyder GL, Higashi H, Nairn AC, Greengard P (2000) Amplification of dopaminergic signaling by a positive feedback loop. Proc Natl Acad Sci USA 97 12840-12845. 

Various drugs are employed therapeutically to influence dopaminergic signal transmission. 

Psychostimulants have been demonstrated to affect dopaminergic signaling by altering DAT and VMAT function (Fleckenstein et al., 2009). Such alterations can be neurotoxic and may provide a role for the monoamine transporters in Parkinson s disease (Fleckenstein et al., 2009). 

Due to the importance of dopaminergic signalling in TD development, and the suspected role of the dopamine D3 receptor (DRD3) in antipsychotic drug action, at least 20 studies have investigated... 

Increased Dopaminergic Signaling in an Animal Model of Parkinson Disease... 

PLA2 is involved in dopaminergic signaling via the D2 receptor. The density of this receptor is increased in basal ganglia circuitry in Parkinsons disease (Cooper et ah, 1996 Guttman, 1992 Schermanet ah. 1989 Graham. 1990 3706). A chronic unilateral lesion... 

Prolactin has no therapeutic uses. Hyperprolactinemia is a relatively common endocrine abnormality that most often is caused by prolactin-secreting pituitary adenomas. Hyperprolactinemia also can result from hypothalamic or pituitary diseases that interfere with the delivery of inhibitory dopaminergic signals primary hypothyroidism associated with increased TRH levels renal failure treatment with dopamine receptor antagonists. Manifestations of prolactin excess in women include galactorrhea, amenorrhea, and infertihty. in men, hyperprolactinemia causes loss of libido, impotence, and infertility. 

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