Dopamine is a key neuromodulatory transmitter in the brain. It acts through dopamine receptors to affect changes in neural activity, gene expression, and behavior. In songbirds, dopamine is released into the striatal song nucleus Area X, and the levels depend on social contexts of undirected and directed singing. This differential release is associated with differential expression of activity-dependent genes, such as egr1 (avian zenk), which in mammalian brain are modulated by dopamine receptors. Here we cloned from zebra finch brain cDNAs of all avian dopamine receptors: the D1 (D1A, D1B, D1D) and D2 (D2, D3, D4) families. Comparative sequence analyses of predicted proteins revealed expected phylogenetic relationships, in which the D1 family exists as single exon and the D2 family exists as spliced exon genes. In both zebra finch and chicken, the D1A, D1B, and D2 receptors were highly expressed in the striatum, the D1D and D3 throughout the pallium and within the mesopallium, respectively, and the D4 mainly in the cerebellum. Furthermore, within the zebra finch, all receptors, except for D4, showed differential expression in song nuclei relative to the surrounding regions and developmentally regulated expression that decreased for most receptors during the sensory acquisition and sensorimotor phases of song learning. Within Area X, half of the cells expressed both D1A and D2 receptors, and a higher proportion of the D1A-only-containing neurons expressed egr1 during undirected but not during directed singing. Our findings are consistent with hypotheses that dopamine receptors may be involved in song development and social context-dependent behaviors. J. Comp. Neurol. 518:741–769, 2010. © 2009 Wiley-Liss, Inc.

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Dopamine receptors in a songbird brain

The avian hippocampal formation (HF) and mammalian hippocampus share a similar functional role in spatial cognition, but the underlying neuronal mechanisms allowing the functional similarity are incompletely understood. To understand better the organization of the avian HF and its transmitter receptors, we analyzed binding site densities for glutamatergic AMPA, NMDA, and kainate receptors; GABAA receptors; muscarinic M1 , M2 and nicotinic (nACh) acetylcholine receptors; noradrenergic α1 and α2 receptors; serotonergic 5-HT1A receptors; dopaminergic D1/5 receptors by using quantitative in vitro receptor autoradiography. Additionally, we performed a modified Timm staining procedure to label zinc. The regionally different receptor densities mapped well onto seven HF subdivisions previously described. Several differences in receptor expression highlighted distinct HF subdivisions. Notable examples include 1) high GABAA and α1 receptor expression, which rendered distinctive ventral subdivisions; 2) high α2 receptor expression, which rendered distinctive a dorsomedial subdivision; 3) distinct kainate, α2 , and muscarinic receptor densities that rendered distinctive the two dorsolateral subdivisions; and 4) a dorsomedial region characterized by high kainate receptor density. We further observed similarities in receptor binding densities between subdivisions of the avian and mammalian HF. Despite the similarities, we propose that 300 hundred million years of independent evolution has led to a mosaic of similarities and differences in the organization of the avian HF and mammalian hippocampus and that thinking about the avian HF in terms of the strict organization of the mammalian hippocampus is likely insufficient to understand the HF of birds.

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Distribution of neurotransmitter receptors and zinc in the pigeon (Columba livia) hippocampal formation: A basis for further comparison with the mammalian hippocampus

A key brain site in the control of male sexual behavior is the medial pre-optic area (mPOA) where dopamine stimulates both D1 and D2 receptor subtypes. Research completed to date in Japanese quail has only utilized systemic injections and therefore much is unknown about the specific role played by dopamine in the brain and mPOA in particular. The present study investigated the role of D1 and D2 receptors on male sexual behavior by examining how intracerebroventricular injections and microinjections into the mPOA of D1 and D2 agonists and antagonists influenced appetitive and consummatory aspects of sexual behavior in male quail. Experiments 1 and 2 investigated the effects of intracerebroventricular injections at three doses of D1 or D2 agonists and antagonists. The results indicated that D1 receptors facilitated consummatory male sexual behavior, whereas D2 receptors inhibited both appetitive and consummatory behaviors. Experiment 3 examined the effects of the same compounds specifically injected in the mPOA and showed that, in this region, both receptors stimulated male sexual behaviors. Together, these data indicated that the stimulatory action of dopamine in the mPOA may require a combined activation of D1 and D2 receptors. Finally, the regulation of male sexual behavior by centrally infused dopaminergic compounds in a species lacking an intromittent organ suggested that dopamine action on male sexual behavior does not simply reflect the modulation of genital reflexes due to general arousal, but relates to the central control of sexual motivation. Together, these data support the claim that dopamine specifically regulates male sexual behavior.

/pdf/differential-effects-of-central-injections-of-d1-and-d2-2umha7gx6j.pdf

Differential effects of central injections of D1 and D2 receptor agonists and antagonists on male sexual behavior in Japanese quail

Social context often has profound effects on behavior, yet the neural and molecular mechanisms which mediate flexible behavioral responses to different social environments are not well understood. We used the African cichlid fish, Astatotilapia burtoni, to examine aggressive defense behavior across three social contexts representing different motivational states: a reproductive opportunity, a familiar male and a neutral context. To elucidate how differences in behavior across contexts may be mediated by neural gene expression, we examined gene expression in the preoptic area, a brain region known to control male aggressive and sexual behavior. We show that social context has broad effects on preoptic gene expression. Specifically, we found that the expression of genes encoding nonapeptides and sex steroid receptors are upregulated in the familiar male context. Furthermore, circulating levels of testosterone and cortisol varied markedly depending on social context. We also manipulated the D2 receptor (D2R) in each social context, given that it has been implicated in mediating context-dependent behavior. We found that a D2R agonist reduced intruder-directed aggression in the reproductive opportunity and familiar male contexts, while a D2R antagonist inhibited intruder-directed aggression in the reproductive opportunity context and increased aggression in the neutral context. Our results demonstrate a critical role for preoptic gene expression, as well as circulating steroid hormone levels, in encoding information from the social environment and in shaping adaptive behavior. In addition, they provide further evidence for a role of D2R in context-dependent behavior.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/gbb.12389

Social context affects behavior, preoptic area gene expression, and response to D2 receptor manipulation during territorial defense in a cichlid fish

Dopamine (DA) transmission in the medial preoptic area (mPOA) plays a critical role in the control of appetitive sexual behaviour in the female rat. We have shown previously that a DA D1 receptor (D1R)-mediated excitatory state appears to occur in females primed with estradiol benzoate (EB) and progesterone (P), whereas a DA D2 receptor (D2R)-mediated inhibitory state appears to occur in females primed only with EB. The present experiment employed three techniques to better understand what changes occur to DA receptors (DARs) in the mPOA under different hormonal profiles. Ovariectomized females were randomly assigned to one of three steroid treatment groups: EB + P (10 and 500 μg, respectively), EB + Oil, or the control (Oil + Oil), with hormone injections administered at 48 and 4 h prior to euthanizing. First, the number of neurons in the mPOA that contained D1R or D2R was assessed using immunohistochemistry. Second, the mPOA and two control areas (the prelimbic cortex and caudate putamen) were analysed for DAR protein levels using western blot, and DAR functional binding levels using autoradiography. Ovarian steroid hormones affected the two DAR subtypes in opposite ways in the mPOA. All three techniques supported previous behavioural findings that females primed with EB have a lower D1R : D2R ratio, and thus a D2R-mediated system, and females primed with EB + P have a higher D1R : D2R ratio, and thus a D1R-mediated system. This provides strong evidence for a DA-driven pathway of female sexual motivation, desire, and behaviour that is modified by different hormone priming regimens.

Ovarian steroids alter dopamine receptor populations in the medial preoptic area of female rats: implications for sexual motivation, desire, and behaviour.

Evidence has accumulated that the regulation of male sexual behavior by dopamine might not be the same in Japanese quail (and perhaps all birds) as it is in mammals. For example, the non-selective dop

Species Differences in the Relative Densities of D1- and D2-Like Dopamine Receptor Subtypes in the Japanese Quail and Rats: An in vitro Quantitative Receptor Autoradiography Study

Hayley K. Kleitz

Papers

Species Differences in the Relative Densities of D1- and D2-Like Dopamine Receptor Subtypes in the Japanese Quail and Rats: An in vitro Quantitative Receptor Autoradiography Study