Aromatase inhibition blocks the activation and sexual differentiation of appetitive male sexual behavior in Japanese quail

Two experiments investigated the role of estrogens in the activation and sexual differentiation of appetitive sexual behavior (ASB) in Japanese quail (Coturnix japonica) as measured by a learned social proximity response. Injection of the aromatase inhibitor R767 13 in castrated, testosterone (T)-treated male quail completely suppressed ASB, confirming that, like consummatory sexual behavior, ASB is mediated by T aromatization. ASB is not observed in female quail, even if they are treated with T as adults. The role of embryonic estrogens in the sexual differentiation of ASB was tested by blocking estrogen synthesis in ovo. Control male and T-treated female quail deprived of estrogens during embryonic life learned the social proximity response used to assess ASB, whereas control female quail did not, despite the presence of high T. Thus, ASB is demasculinized by the action of embryonic estrogens during ontogeny as is consummatory behavior.     

Dopamine release in the medial preoptic area is related to hormonal action and sexual motivation.

To help elucidate how general the role of dopamine (DA) release in the medial preoptic area (mPOA) is for the activation of male sexual behavior in vertebrates, we recently developed an in vivo microdialysis procedure in the mPOA of Japanese quail. Using these techniques in the present experiment, the temporal pattern of DA release in relation to the precopulatory exposure to a female and to the expression of both appetitive and consummatory aspects of male sexual behavior was investigated. Extracellular samples from the mPOA of adult sexually experienced male quail were collected every 6 min before, while viewing, while in physical contact with, and after exposure to a female. In the absence of a precopulatory rise in DA, males failed to copulate when the barrier separating them from the female was removed. In contrast, males that showed a substantial increase in mPOA DA during precopulatory interactions behind the barrier, copulated with females after its removal. However, there was no difference in DA during periods when the quail were copulating as compared to when the female was present but the males were not copulating. In addition, we show that precopulatory DA predicts future DA levels and copulatory behavior frequency. Furthermore, the size of the cloacal gland, an accurate indicator of testosterone action, is positively correlated with precopulatory DA. Taken together, these results provide further support for the hypothesis that DA action in the mPOA is specifically linked to sexual motivation as compared to copulatory behavior per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potential pathogenic mechanisms of periodontitis associated pregnancy complications

The authors investigated the behavioral actions of vasotocin (VT) in castrated testosterone-treated male Japanese quail. The appetitive and consummatory components of sexual behavior as well as the occurrence frequency of crows were inhibited, in a dose-dependent manner, by injections of VT. The authors observed opposite effects after injection of the V1 receptor antagonist, dPTyr(Me)AVP. Lower doses of VT were more active after central than after systemic injection, and effects of systemic injections of VT were blocked by a central injection of dPTyr(Me)AVP. The behavioral inhibition was associated with a modified diuresis after systemic but not central injection. These results provide direct evidence that VT affects male sexual behavior in quail by a direct action on the brain independent of its peripheral action on diuresis.     

Systemic and intracerebroventricular injections of vasotocin inhibit appetitive and consummatory components of male sexual behavior in Japanese quail.

The authors investigated the behavioral actions of vasotocin (VT) in castrated testosterone-treated male Japanese quail. The appetitive and consummatory components of sexual behavior as well as the occurrence frequency of crows were inhibited, in a dose-dependent manner, by injections of VT. The authors observed opposite effects after injection of the V1 receptor antagonist, dPTyr(Me)AVP. Lower doses of VT were more active after central than after systemic injection, and effects of systemic injections of VT were blocked by a central injection of dPTyr(Me)AVP. The behavioral inhibition was associated with a modified diuresis after systemic but not central injection. These results provide direct evidence that VT affects male sexual behavior in quail by a direct action on the brain independent of its peripheral action on diuresis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Is sexual motivational state linked to dopamine release in the medial preoptic area?

The medial preoptic area (mPOA) is a key site for the dopaminergic enhancement of male sexual behavior. Dopamine release increases in the rat mPOA with mating, supporting the critical stimulatory role played by preoptic dopamine on male sexual behavior. However, it has been questioned whether dopamine is specifically related to the occurrence of male sexual behavior and not simply involved in general arousal. To address this question, we asked whether dopamine release in the mPOA is linked to the production of male sexual behavior in Japanese quail (Coturnix japonica), a species that exhibits a much shorter temporal pattern of copulation than rats and does not have an intromittent organ, resulting in a very different topography of their sexual response. Extracellular samples from the mPOA of adult sexually experienced male quail were collected every 6 min before, during, and after exposure to a female using in vivo microdialysis and analyzed using high-performance liquid chromatography with electrochemical detection. Extracellular dopamine significantly increased in the presence of a female and returned to baseline after removal of the female. However, quail that failed to copulate did not display this increased release. These findings indicate that it is not solely the presence of a female that drives dopamine release in males, but how a male responds to her. Furthermore, in quail that copulated, dopamine release did not change in samples collected during periods of no copulation. Together, these findings support the hypothesis that dopamine action in the mPOA is specifically linked to sexual motivation and not only to copulatory behavior or physical arousal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Appetitive as well as consummatory aspects of male sexual behavior in quail are activated by androgens and estrogens.

Appetitive male sexual behavior was measured in male quail with the use of a learned social proximity procedure that quantified the time spent by a male in front of a window providing a view of a female that was subsequently released into the cage, providing an opportunity for copulation. The learned response is not acquired by castrated males but can be acquired when castrates are treated with testosterone (T) or with the synthetic estrogen diethylstilbestrol or with the endogenous estrogen 17β-estradiol. Only birds that become sexually active acquire the response. Conversely, birds in which the consummatory copulatory behavior is disrupted by treatment with the antiestrogen tamoxifen lose the anticipatory response. These results demonstrate that appetitive sexual behavior is, like copulation, activated by T and by estrogens. This suggests that intracerebral aromatization of T also plays a critical role in the activation of this behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine agonist-induced hypothermia and disruption of prepulse inhibition: evidence for a role of D3 receptors?

The dopamine D3/D2 receptor agonists 7-OH-DPAT, quinpirole, quinelorane, and PD128907, the mixed dopamine agonist apomorphine, the D2 agonist bromocriptine, and the D1/D5 agonist SKF38393 were examined in models of hypothermia and prepulse inhibition (PPI) in Wistar rats. As dopamine agonist-induced hypothermia has been proposed as a model of D3 receptor function, and dopamine agonists are known to disrupt PPI, drug potencies to induce hypothermia were established and compared with doses necessary to disrupt PPI. 7-OH-DPAT, quinpirole, quinelorane, PD128907, and apomorphine, reduced body temperature and disrupted PPI with a similar rank order of potency (quinelorane > quinpirole = 7-OH-DPAT > PD128907 = apomorphine). Bromocriptine and SKF38393 were ineffective in both models. In a separate study, the dopamine reuptake inhibitors cocaine and GBR 12909 had no effect on PPI. In a final set of studies, the D2/D3 antagonist raclopride blocked both 7-OH-DPAT-induced hypothermia and 7-OH-DPAT-induced PPI disruption. The 5-HT1A antagonist WAY 100,135, and the peripheral D2-like antagonist domperidone had no effect. These findings suggest that the hypothermia and PPI disruptions seen with some of these dopamine agonists may be mediated by central D3 receptors; however, only studies using more selective dopamine receptor ligands can definitively rule out effects at the D2 or D4 receptors.     

A comparative approach to the study of dopamine and male sexual behavior: What can Japanese quail teach us? A reply to Pfaus (2010).

One of the most robust findings about dopamine (DA) is that the stimulation of dopaminergic systems promotes the activation of male sexual behavior. The commentary by Pfaus (see record 2010-24688-009) included a thorough review of studies of DA and male sexual behavior. We agree with him that the release of DA in the preoptic region in male quail in response to females and in association with the exhibition of male sexual behavior appears to be highly conserved and that it seems to have evolved very early in the evolutionary history of the vertebrate brain. However, additional data have been collected indicating that there may be significant species differences in the dopaminergic regulation of male behavior in quail compared with rats. In this response, we take the opportunity to make a few broader points about DA and male sexual behavior in light of other studies that have been conducted in birds and introduce some interesting taxonomic variation that is still not well understood. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of stable cell lines expressing different subtypes of GABAA receptors

In the quail preoptic area (POA) anatomical and pharmacological data suggest that catecholamines may be implicated in the control of testosterone (T) aromatization into estrogens. The biochemical mechanism(s) mediating this control of the enzyme activity is (are) however unexplored. The present studies were carried out to investigate whether the catecholamines, dopamine (DA) and norepinephrine (NE) are able to directly affect aromatase activity (AA) measured during in vitro incubations of POA homogenates. AA was quantified in the POA-hypothalamus of adult male Japanese quail by measuring the tritiated water production from [1beta-3H]-androstenedione. Enzyme activity was linear as a function of the incubation time and of the protein content of homogenates. It exhibited a typical Michaelis-Menten kinetics, with an apparent Km of 2.8 nM and a Vmax of 266.6 fmol h(-1) mg wet weight(-1). AA was then measured at a substrate concentration of 25 nM in the presence of catecholamines and some of their receptor agonists or antagonists, at two concentrations, 10(-3) and 10(-6) M. Norepinephrine and prazosin (alpha1-adrenergic antagonist) had no or very limited effects on AA at both concentrations. In contrast, DA and some D1 and/or D2 receptor agonists (apomorphine[D1/D2], SKF-38393 [D1] and RU-24213 [D2]) depressed AA by 40 to 70% at the 10(-3) M concentration. One D2 receptor antagonist also produced a major inhibition of AA (sulpiride) while other antagonists either had no significant effect or only produced moderate decreases in enzyme activity (SCH-23390 [D1], spiperone [D2], pimozide [D2]) as did two DA indirect agonists, amfonelic acid and nomifensine. The inhibitory effect of the agonists was not antagonized by the less active antagonists, SCH-23390 [D1] or spiperone [D2]. Taken together these results suggest that the inhibitory effects do not involve specific binding of DA or its agonists/antagonists to dopaminergic receptors mediating changes in cAMP concentration. This conclusion is also supported by the observation that addition of dibutyryl cAMP did not change brain AA. It appears more likely that DA and dopaminergic drugs inhibit AA by a direct effect on the enzyme, as suggested by the competitive nature of DA and SKF-38393 inhibition of AA (Ki's of 59 and 84 microM, respectively). The functional significance of this effect should still be demonstrated but this mechanism may represent an important physiological pathway through which neurotransmitters could rapidly affect steroid-dependent processes such as the neural synthesis of estrogens. This would provide a mean by which environmental stimuli could affect reproductive behavior and physiology.     

Dopamine: Helping males copulate for at least 200 million years: Theoretical comment on Kleitz-Nelson et al. (2010).

Brain dopamine (DA) systems are implicated in a variety of behavioral responses and clinical syndromes, including sex, drug addiction, feeding, satiety, sleep, wakefulness, arousal, attention, reward, decision-making, depression, anxiety, psychosis, and movement disorders. The paper in this issue (see record 2010-24688-004) by Kleitz-Nelson, Dominguez, and Ball (2010) shows how DA release in the medial preoptic area of male quail are activated in an androgen-dependent manner during appetitive and consummatory phases of sexual behavior, similar to that reported previously in male rats. Those data suggest that the steroid-dependent role of hypothalamic DA in male sexual behavior has been conserved through evolutionary time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential influence of D1 and D2 dopamine receptors on acute opiate withdrawal in guinea-pig isolated ileum

1. The effects exerted by D1 and D2 dopamine agonists and antagonists on the acute opiate withdrawal induced by mu- and kappa-receptor agonists were investigated in vitro. 2. Following a 4 min in vitro exposure to morphine (moderately selective mu-agonist), [D-Ala2, Me-Phe4, Gly-ol5]enkephalin (DAMGO, highly selective mu-agonist) or U-50488H (highly selective kappa-agonist) the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. 3. The non-selective dopamine receptor antagonist haloperidol when added before or after the opioid agonists, was able dose-dependently to prevent or to reverse the naloxone-induced contracture after exposure to mu- (morphine and DAMGO) and kappa- (U-50488H) opioid agonists. The non-selective dopamine receptor agonist, apomorphine, was able to exert the same effects only at the highest concentration used. 4. The selective D2 dopamine receptor antagonist, sulpiride, was also able to reduce dose-dependently both mu- and kappa-opioid withdrawal, whereas the D1-receptor selective antagonist SCH 23390 did not affect either mu- or kappa-opioid withdrawal. 5. Bromocriptine, a D2 selective dopamine receptor agonist was able to increase significantly, and in a concentration-dependent manner, the naloxone-induced contracture by mu- and kappa-opioid agonists, whereas SKF 38393, a D1 selective dopamine receptor agonist, increased only the withdrawal after morphine or U50-488H. 6. Our data indicate that both D1 and D2 dopamine agonists and antagonists are able to influence opiate withdrawal in vitro, suggesting an important functional interaction between the dopaminergic system and opioid withdrawal at both the mu- and kappa-receptor level. 7. Furthermore, the ability of sulpiride to block strongly opiate withdrawal when compared to SCH 23390, as well as the effect of bromocriptine to increase opiate withdrawal suggest that D2 dopamine receptors may be primarily involved in the control of opiate withdrawal.     

Motor response to a dopamine D3 receptor preferring agonist compared to apomorphine in levodopa-primed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys

The profile of dopamine receptor subtype activation contributing to the therapeutic efficacy and motor response complications of levodopa (nonselective pro-agonist) in Parkinson's disease remains unclear. Potent, selective, short-acting dopamine D2 receptor subfamily agonists show good antiparkinsonian efficacy but produce dyskinesias comparable to levodopa. Nonetheless, agonists displaying higher affinity for dopamine receptors other than the D2 subtype may have a better therapeutic index. To clarify this issue, we compared the nonselective dopamine D1/D2 receptor subfamilies agonist apomorphine to the dopamine D3 receptor preferring agonist [R-(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4 , 3-b]-1,4-oxazin-9-ol] (PD 128,907) in 6 levodopa-primed , 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian monkeys with reproducible dyskinesias. Single s.c. dosing with the lowest fully effective dose of apomorphine (averaging 27.9 +/- 4.5 microg/kg) and PD 128,907 (averaging 41.7 +/- 4.4 microg/kg) yielded equivalent antiparkinsonian efficacy on the behavioral scale and portable activity monitoring used. A comparable significant dose-dependent increase in the response magnitude and duration was seen with two higher doses. The severity of dyskinesia was also similar between the two drugs. When the lower dose for each drug was administered six times at a fixed 90-min interval, both drugs remained efficacious with no significant tolerance observed. The D3 receptor preferring antagonist U-99194A significantly reduced the motor effects of both apomorphine and PD 128,907. Thus, increased D3 receptor tone does not acutely ameliorate dyskinesias in levodopa-primed parkinsonian monkeys. Given the reported lack of affinity of PD 128,907 for central D1 receptors, our data support the concept that the pharmacological activation of D1 receptors is not mandatory for relief of parkinsonism and production of dyskinesia.     

Alterations of male sexual behavior by learned aversions to hamster vaginal secretion.

32 male hamsters poisoned after their 1st adult exposure to the vaginal secretion of female hamsters became hesitant to approach and ingest the secretion. The same aversion-training procedure also altered the responses of males to estrous females, changing the latency, frequency, and duration of a variety of behaviors that are commonly taken as indexes of sexual attraction or arousal and of copulatory performance. Results suggest that the aversions to vaginal secretion alter the perceived meaning of the secretion for male hamsters, and analysis of the correlations between various measures of sexual arousal and performance support the hypothesis that separate mechanisms underlie the effects of the secretion on appetitive and consummatory sexual behavior. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of dopaminergic drugs on innate pheromone-mediated reward in female mice: A new case of dopamine-independent "liking."

Male sexual pheromones are innately rewarding to adult female mice, but the role of dopamine in this natural reward is unknown. The authors have tackled this issue by assessing the effects of intraperitoneal injections of dopamine D? (SCH 23390, 0.02- 0.05mg/kg) and D? (sulpiride, 20.00 mg/kg) antagonists, a dopamine releasing agent (amphetamine, 0.50 -2.00 mg/kg), and D? (SKF 38393, 10.00 -20.00 mg/kg) and D? (quinpirole, 0.20 -1.00 mg/kg) agonists on the chemoinvestigation displayed by female mice in male- versus female-soiled bedding 2-choice tests. Dopamine antagonists and quinpirole failed to affect the unconditioned preference displayed by females towards male chemosignals, whereas both amphetamine and SKF 38393 abolished it. Finally, D? and D? antagonists did not block the induction of operant place conditioning by male chemosignals. As the female mice were tested in their first encounter with male sexual pheromones, their behavior can only be influenced by the "liking" component of reward. Therefore, the results suggest that dopamine mediates neither the hedonic properties of male sexual pheromones nor the acquisition of conditioned place preference. However, dopamine acting on D1 receptors might inhibit female mice attraction towards male chemosignals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adenovirus-mediated gene transfer is augmented in basilar and carotid arteries of heritable hyperlipidemic rabbits

OBJECTIVE: Regional presynaptic dopaminergic function and its regulation by dopamine agonists in different stages of PD can be measured by L-[11C]dopa and PET. In the current investigation, we studied the effects of therapeutic apomorphine on L-[11C]dopa uptake in patients with early and advanced PD. BACKGROUND: With disease progression and chronic dopamine agonist treatment, motor response complications supervene in a majority of PD patients. It is assumed that both presynaptic and postsynaptic changes in the dopaminergic system act to modify dopaminergic efficacy. METHODS: Patients with early and advanced stages of PD were included in the study. All patients were investigated twice with PET and L-[11C]dopa drug free and during a subsequent standardized therapeutic apomorphine infusion. RESULTS: Subregional analysis of the striatum showed differences in the effects of apomorphine infusion on the L-[11C]dopa influx rate in the two patient categories. In patients with early and uncomplicated PD, apomorphine infusion decreased the L-[11C]dopa influx rate. This decrease was most pronounced in the dorsal part of the putamen. In advanced PD patients, apomorphine did not affect the striatal L-[11C]dopa influx rate. CONCLUSIONS: We suggest that in mild and stable PD an upregulated presynaptic inhibitory feedback regulation, particularly in the dorsal putamen, acts to maintain congruity within the dopaminergic system in response to antiparkinsonian medication. However, this inhibitory feedback regulation is diminished with the progression of nigrostriatal degeneration and chronic dopamine agonist treatment.     

In vitro induction of apoptosis or differentiation by dopamine in an immortalized olfactory neuronal cell line

A new neuronal cell line was generated by transfection of rat olfactory epithelium with immortalizing recombinant oncogene E1A of adenovirus-2. The resulting 13.S.1.24 line of transformed cells expressed an antigenic phenotype of olfactory neuronal progenitors. Addition of dopamine to 13.S.1.24 cultures induced reduction of cell number within 2 days. Two hallmarks of apoptosis were detected in dopamine-treated cultures: internucleosomal DNA fragmentation and nuclear condensation. Dopamine did not alter the cell proliferation rate, as assessed by [3H]thymidine incorporation. Dopamine also stimulated differentiation of surviving 13.S.1.24 cells into bipolar olfactory marker protein-immunoreactive neurons. Time-dependency assessments over 1 week of treatment indicated that apoptosis and differentiation induced by dopamine were concomitant. Both apoptosis and differentiation triggered by dopamine were dose-dependent, half-maximal effects being obtained with approximately 10 microM dopamine. Mediation of both effects by dopaminergic D2 receptors was supported by several observations: active dopamine doses in micromolar ranges, quinpirole agonism and eticlopride antagonism, D2-characteristic rank order of potency among the three agonists tested, and specific binding of a selective D2-like radioligand to 13.S.1.24 cells. The present data altogether indicated that dopamine commits immortalized olfactory neuronal cells in vitro either to apoptosis or to olfactory-like differentiation via D2 dopaminergic receptors.     

Light microscope autoradiography of peripheral dopamine receptor subtypes

Radioligand binding assay techniques associated with light microscope autoradiography were used for investigating the pharmacological profile and the micro anatomical localization of peripheral dopamine receptor subtypes. In systemic arteries, the predominant dopamine D1-like receptor belongs to the D5 (or D1B) subtype. It is located within smooth muscle of the tunica media. In pulmonary arteries, dopamine D1-like receptors have primarily an endothelial localization and belong to the dopamine D1 (or D1A) receptor subtype. Both systemic and pulmonary arteries express a dopamine D2-like receptor belonging to the D2 receptor subtype. It has a prejunctional localization in the majority of vascular beds investigated. In cerebral, coronary and mesenteric arteries, it has also an endothelial localization. In the heart, a dopamine D4 receptor was identified. It is expressed by atrial tissue and has a widespread distribution overall atrial musculature. The kidney expresses both dopamine D1-like and D2-like receptors. Renal dopamine D1-like receptors have a vascular and tubular localization. The majority of these sites belongs to the D5 receptor subtype. A smaller D1 receptor population has primarily a tubular localization. Renal dopamine D2-like receptors belong to the dopamine D3 subtype and in lesser amounts to the D2 and D4 receptor subtypes. Renal dopamine D3 receptor has to a greater extent a tubular localization, whereas the D4 receptor is located within glomerular arterioles. The above results suggest that radioligand binding assay and autoradiographic techniques, if performed in the presence of compounds displaying specific receptor subtype selectivity, may contribute to characterize, mainly from a quantitative point of view, peripheral dopamine receptors.     

Lack of opioid or dopaminergic effects on unconditioned sexual incentive motivation in male rats.

The effects of dopaminergic and opioidergic drugs on sexual incentive motivation were evaluated in sexually inexperienced male rats subjected to a choice procedure. Various parameters of ambulatory activity were recorded as well. Two drugs stimulating dopaminergic neurotransmission, amphetamine and apomorphine, failed to affect sexual incentive motivation, although ambulatory activity was enhanced by amphetamine. The dopamine antagonist cis(Z)-flupenthixol reduced sexual incentive motivation, but only at a dose that severely disrupted motor function. Morphine had marginal effects on sexual motivation but reduced ambulatory activity. These effects were not reduced by a peripheral opioid antagonist, methylnaloxone. Loperamide, a peripheral opioid agonist, reduced sexual motivation through an opioid-independent action. Naloxone was ineffective. Neither dopamine nor opioids seem to be important for sexual incentive motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blockade of subthalamic dopamine D1 receptors elicits akinesia in rats

The role of dopamine in the subthalamic nucleus to control motor behaviour was investigated in rats using bilateral microinfusions of the dopamine D1 receptor antagonist SCH23390 and the dopamine D2 receptor antagonist S(-)-sulpiride. Selective blockade of subthalamic D1 receptors, but not of D2 receptors, produced catalepsy. These findings suggest that dopamine D1 receptors within the subthalamic nucleus play a prominent role in the regulation of motor functions. Furthermore, the data point to the possibility that a reduced dopaminergic tone at subthalamic dopamine D1 receptors might contribute to akinesia in Parkinson's disease.     

Functional role and pharmacological regulation of the dopaminergic system of the brain

The dopaminergic systems of the brain are thought to play a major role in the regulation of motor, cognitive, neuroendocrine functions and in the pathogenesis of several pathological conditions, including neurodegenerative diseases, affective disorders, schizophrenia, drug addiction, etc. Functional, biochemical, and pharmacological heterogeneity of dopamine receptors, which were divided into D1-like (D1 and D5 subtypes) and D2-like (D2, D3, and D4) families of receptors, has been postulated. The paper concerns the recent advances in the study of the structure and function of two main dopaminergic brain systems, i.e. nigrostriatal and mesolimbic. The problem of autoreceptor regulation of dopaminergic neurotransmission, particularly the processes of dopamine synthesis, release, and metabolism is discussed. The involvement of D2 and D3 dopamine autoreceptors in the control of these processes and differences in the mode of action of typical neuroleptics are analyzed. It is hypothesized that dopamine D3 autoreceptor is preferentially involved in the regulation of dopamine release while D2 one is responsible for the control of dopamine synthesis and metabolism in rat basal ganglia in vivo.