Risky decision making involves the ability to weigh risks and rewards associated with different options to make adaptive choices. Previous work has established a necessary role for the basolateral amygdala (BLA) in mediating effective decision making under risk of punishment, but the mechanisms by which the BLA mediates this process are less clear. Because this form of decision making is profoundly sensitive to dopaminergic (DA) manipulations, we hypothesized that DA receptors in the BLA may be involved in risk-taking behavior. To test this hypothesis, male and female Long-Evans rats were trained in a decision-making task in which rats chose between a small, safe food reward and a larger food reward that was associated with a variable risk of footshock punishment. Once behavioral stability emerged, rats received intra-BLA infusions of ligands targeting distinct dopamine receptor subtypes prior to behavioral testing. Intra-BLA infusions of the dopamine D2 receptor (D2R) agonist quinpirole decreased risk taking in females at all doses, and this reduction in risk taking was accompanied by an increase in sensitivity to punishment. In males, decreased risk taking was only observed at the highest dose of quinpirole. In contrast, intra-BLA manipulations of dopamine D1 or D3 receptors (D1R and D3R, respectively) had no effect on risk taking. Considered together, these data suggest that differential D2R sensitivity in the BLA may contribute to the well-established sex differences in risk taking. Neither D1Rs nor D3Rs, however, appear to contribute to risky decision making in either sex.

01 Oct 2024·Toxicological Research

Therapeutic strategies for colorectal cancer: antitumor efficacy of dopamine D2 receptor antagonists

Review

Author: Chun, Kyung-Soo ; Joo, Sang Hoon

Colorectal cancer (CRC) is one of the leading causes of death, accounting for more than half a million deaths annually. Even worse, an increasing number of cancer cases are diagnosed yearly, and two and a half million new cancer cases are estimated to be diagnosed in 2035. Some antipsychotic drugs, especially those targeting dopamine receptor (DR) D2, demonstrated anticancer activity. Studies have revealed the potential of DRD2 antagonists as anticancer therapeutics, whether alone or as an adjuvant, in treating breast cancer, lung cancer, and others. Emerging evidences indicate DRD2 is involved in the CRC biology, and the association between DRD2 and CRC could be utilized in treating CRC. This study selected DRD2 antagonists with anticancer activity to elucidate the possibility of DRD2 antagonists as new therapeutics for treating CRC.

01 Oct 2024·Experimental Eye Research

Impaired dopamine signaling in early diabetic retina: Insights from D1R and D4R agonist effects on whole retina responses

Article

Author: Eggers, Erika D ; Wellington, Andrea J ; Filicetti, Kyle ; MacIsaac, Angela R

The retina has low dopamine levels early in diabetes. To determine how low dopamine levels affected dopamine signaling, the effects of dopamine receptor agonists and mRNA localization were measured after 6 weeks of diabetes. Whole retina ex vivo electroretinogram (ERG) recordings were used to analyze how dopamine type 1 receptor (D1R) and type 4 (D4R) agonists change the light-evoked retinal responses of non-diabetic and 6-week diabetic (STZ injected) mouse retinas. Fluorescence in situ hybridization was utilized to analyze D4R and D1R mRNA locations and expression levels. D4R activation reduced A- and B-wave ERG amplitudes and increased B-wave implicit time and rise-time in the non-diabetic group without a corresponding change in the diabetic group. D1R activation increased B-wave rise-time and oscillatory potential peak time in the non-diabetic group also with no change in the diabetic group. The lack of responsivity to D1R or D4R agonists shows an impairment of dopamine signaling in the diabetic retina. D4R mRNA was found primarily in the outer nuclear layer where photoreceptor cell bodies reside. D1R mRNA was found in the inner nuclear layer and ganglion cell layer that contain bipolar, amacrine, horizontal and ganglion cells. There was no change in D4R or D1R mRNA expression between the non-diabetic and diabetic retinas. This suggests that the significant dopamine signaling changes observed were not from lower receptor expression levels but could be due to changes in dopamine receptor activity or protein levels. These studies show that changes in retinal dopamine signaling could be an important mechanism of diabetic retinal dysfunction.

100 Deals associated with D2 receptor agonists (University of Toronto)

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Indication	Highest Phase	Country/Location	Organization	Date
Diagnostic agents	Preclinical	IN	University of Toronto	16 Jun 2005

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