Dopamine Receptor Concentrations Research Articles

Adrenocortical hormone status affects responses to dopamine receptor agonists

The effects of altered adrenocortical hormone status were investigated on hypothermic and behavioural responses elicited following systemically administered apomorphine or LY171555. Hormonal status was modified by surgical adrenalectomy, followed by subsequent replacement therapy with corticosterone, and by chronic corticosterone treatment of intact rats, followed by its withdrawal. The incidence of stereotyped sniffing produced by both apomorphine and LY171555 was increased in the adrenalectomized group and decreased following replacement therapy and in intact rats treated with chronic corticosterone, compared with sham-operated animals and saline-treated controls, respectively. Withdrawal of chronic corticosterone treatment in intact rats reversed the effects of the chronic treatment on dopamine-mediated responses. Similar changes were observed in hypothermic responses to the two dopamine agonists. Striatal D-1 and D-2 dopamine receptor concentration and affinity were unaffected by adrenal hormone modification suggesting that corticosterone may act at a site distal to the dopamine receptor to bring about the observed changes in dopamine-mediated behavioural responsiveness.

Modulation of rat striatal membrane fluidity: Effects on age related differences in dopamine receptor concentrations

Rat striatal membrane fluidity and dopamine receptor concentrations were modulated in vitro by ethanol or cholesterol hemisuccinate treatment. In general, available receptor levels are directly proportional to membrane fluidity. However, receptor concentrations remained higher in mature membranes at all levels of fluidity attained. These results suggest that apparent loss of striatal dopamine receptors during aging is not due to membrane sequestration.

Serotonin and dopamine receptors in the rat pituitary gland: autoradiographic identification, characterization, and localization.

S2 serotonin and D2 dopamine receptors were identified, characterized, and localized in rat pituitary gland by quantitative light microscopic autoradiography. [3H]Spiperone was used to localize S2 serotonin and D2 dopamine receptors. A high concentration of D2 dopamine receptors [1 microM 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN)- or sulpiride-displaceable [3H]spiperone binding] was found in the rat intermediate lobe with much lower concentrations present in the anterior and posterior lobes. Significant densities of cinanserin-displaceable [3H]spiperone binding sites (i.e. S2 serotonin receptors) were present in all three lobes of the pituitary gland. [125I]Lysergic acid ([125I]LSD) was used to characterize further and selectively visualize S2 serotonin receptors in the rat pituitary. Data analysis by densitometry showed that [125I]LSD binding the rat intermediate pituitary was saturable and of high affinity with an apparent dissociation constant (Kd) of 1.2 nM. Data from competition studies using a variety of compounds showed a S2 serotonin receptor profile at this [125I]LSD binding site in rat pituitary. The highest concentration of [125I]LSD binding sites was found in the intermediate lobe with progressively lower concentrations present in the posterior and anterior lobes, respectively. There is a uniform pattern of distribution of S2 serotonin and D2 dopamine receptors within each lobe of the rat pituitary gland. The results of the present study provide the first identification of S2 serotonin receptors in the pituitary and confirm the heterogeneous distribution of D2 dopamine receptors within the rat pituitary. These data provide further evidence for the importance of dopamine in regulating pituitary function and suggest a physiological role for serotonin in regulating pituitary hormone secretion.

Hypothyroidism leads to increased dopamine receptor sensitivity and concentration.

Rats treated with iodine-131 were confirmed to be hypothyroid by their reduced baseline core body temperatures, reduced serum thyroxine concentrations and elevated serum thyroid stimulating hormone concentrations. When hypothyroid rats were compared to euthyroid controls they were more sensitive to the effects of apomorphine (1.0 mumol/kg) on stereotypy, operant responding and body temperature and showed a smaller reduction in locomotor activity after injection of haloperidol (0.25 mumol/kg). Receptor binding studies on striatal homogenates indicated that hypothyroid rats had increased concentrations of D2 dopamine receptors but there was no change in the affinity. It is concluded that hypothyroidism increases dopamine receptor sensitivity by increasing receptor concentration.

Reduction of motor behavioral deficits in senescent animals via chronic prolactin administration I. Rotational behavior

The effects of chronic prolactin administration on amphetamine or dopamine (DA) induced rotational behavior was examined in mature (6 month) and senescent (24 month) Wistar rats which were unilaterally lesioned in the left substantia nigra with 6-hydroxydopamine. Prolactin (150 ng/hr) was administered for 7 days via subcutaneously implanted Alzet ® minipumps. Amphetamine (AMPH) (0, 10 μg) or DA (0, 25 μg) was administered through cannula which had been implanted into the right (intact) striatum. Both DA-active agents were given prior to pump implantation and on day 4 of prolactin administration. The AMPH was dissolved in saline (1 μl; pH, 5.5–6.0), while DA was dissolved in N 2 bubbled distilled H 2O (1 μl; pH, 5.5–6.0) and the animals were pretreated with nialamide (50 mg/kg) intraperitoneally 1 hr before DA or DA-vehicle injection. The order of drug administration was counterbalanced within the age groups. Results showed that both groups of animals exhibited higher rotational behavior scores following prolactin treatment. In fact, there was a trend toward greater enhancement of rotational behavior in the senescent animals following prolactin treatment than that seen in mature animals. These results parallel those reported previously wherein it was found that striatal DA receptor concentrations (as assessed with [ 3H]spiperone binding) were higher in prolactin treated mature and senescent animals than in their respective controls. The findings suggest that there is a relationship between increases in the density of striatal DA receptors and improvement in motor performance tasks in senescent animals.

Increased activity of sympatho-adrenomedullary system and decreased renal dopamine receptor content after short-term and long-term sodium loading in rats

We investigated the effects of short-term and long-term sodium loading on the sympathoadrenomedullary system and renal dopamine receptor. Male Wistar rats (n = 30) were raised drinking 1% NaCl for four weeks. Urinary norepinephrine and epinephrine excretion (UNE and UE) were measured before and 1, 2, 4 weeks after sodium loading by the use of high pressure liquid chromatography with fluorescence spectrophotometer. Renal plasma membranes were prepared by the ultracentrifugation method, and maximal binding capacity (Bmax) and dissociation constant (Kd) of renal dopamine receptor were determined by Scatchard analysis using 3-H-spiperone. Sodium loading caused a slight but not significant decrease of free UNE after 1 and 2 weeks then clear increments of total (free + conjugated) UNE, free UE and total UE after 4 weeks. Bmax of renal dopamine receptor did not change after 1 and 2 weeks but significantly decreased after 4 weeks (before: 535.9 fmol/mg X protein, after 4 weeks: 327.2 fmol/mg X protein). Kd of renal dopamine receptor slightly elevated 1 week after sodium loading and then returned to the initial level. These data suggest that short-term sodium loading may suppress the sympathetic activity, but long-term sodium loading may increase the activity of the sympathoadrenomedullary system with the decrease of renal dopamine receptor concentration. Increased catecholamines and decreased renal dopamine after long-term sodium loading may contribute to sodium-dependent hypertension.

Modulation of brain and pituitary dopamine receptors by estrogens and prolactin

1. Ovariectomized rats were treated for 2 weeks with 17β-estradiol (0.0002–100 μg/day). [ 3H] spiperone striatal dopamine receptor binding was maximally increased by 30% after 0.05 μg/day of 17β-estradiol and a similar increase is observed at higher doses. By contrast, plasma prolactin concentrations of these rats are unchanged after 0.05 μg/day and increased after 100 μg/day. A chronic estradiol treatment at very low doses (0.0002–0.001 μg/day) leads to increases in pituitary dopamine receptor binding while plasma prolactin levels are unchanged. At higher doses (1–100 μg/day) binding is decreased and plasma prolactin concentrations are elevated. 2. [ 3H]spiperone striatal dopamine receptor binding is elevated in lactating female rats compared to intact or ovariectomized female rats. 3. Anterior pituitary dopamine receptor concentrations fluctuate during the estrous cycle while striatal dopamine receptors are unchanged. 4. An injection of 30 ng of estradiol, which reproduces the estradiol proestrus surge, leads as in proestrus, to a decrease of anterior pituitary dopamine receptors.

Alterations in the dopaminergic system and behaviour in rats reared on iodine-deficient diets

Male rats raised on an iodine-deficient diet were found to be retarded in growth rate, to have lowered body temperature, and to have poorer memory retention of a passive avoidance task than rats raised on a similar diet but with adequate iodine concentration. In addition, the iodine deficient rats showed increased locomotor activity and sniffing frequency after the dopamine agonist, apomorphine; while their operant performance was inhibited to a greater degree after apomorphine. However, the hypothermic effects of apomorphine were comparable in both iodine-deficient and normal rats. At sacrifice the iodine-deficient rats were found to have significantly depressed thyroxine levels (less than 10% of normal), significantly elevated TSH levels (greater than 700% of normal), and a significantly greater concentration of dopamine receptors in the striatum (28% increase). Thus, rats raised on iodine-deficient diets have considerable behavioural and physiological alterations, including an increased concentration of dopamine receptors.

Localization of dopamine receptors in the rabbit renal artery: a histoautoradiographic study.

The localization of dopamine receptors within rabbit renal artery was studied using 3H-spiroperidol as a label for dopamine receptors and a histoautoradiographic technique. Preliminary radioreceptor binding studies showed that 3H-spiroperidol was bound to sections of renal artery in a manner consistent with the existence of dopamine receptors. In fact the binding was found to be saturable, stereospecific and of high affinity, with a Bmax approximately of 158.3 fmol/mg protein and a Kd of 13.5 nmol/l. The microscopic examination of sections processed for the histoautoradiographic demonstration of 3'-spiroperidol binding sites showed that the distribution of dopamine receptors in the renal artery was widespread. The highest concentration of dopamine receptors was found primarily in the smooth muscle cells of the media and then, in the following order, in endothelial cells of the intima and in fibrous and connective cells of the adventitia. The direct demonstration of dopamine receptors in the media of rabbit renal artery strongly supports the hypothesis that these receptors may be involved in the relaxation of the artery caused by infusion or application of dopamine.

Effect of aging on prolactin regulation of rat striatal dopamine receptor concentrations

Administration of highly purified rat prolactin by miniosmotic pump increases striatal dopamine receptor concentrations in both mature (4–6 months) and senescent (24 months) male Wistar rats. Although receptor levels in untreated rats are about 30% lower in the senescent group, elevated levels following prolactin are not significantly different between ages. Increases in circulating prolactin levels after 7 days of treatment were not detectable at the low concentrations used (150 ng/hr). In fact, there was a trend toward decreases in circulating prolactin concentrations to the same level in both groups after treatment, despite substantially elevated basal levels in many of the senescent rats.

Prolactin and estradiol increase striatal dopamine receptor density in intact, castrated and hypophysectomized rats

1. Ovariectomized female or intact male rats were implanted with three adenohypophyses under the kidney capsule or treated with 17 beta-estradiol (10 micrograms twice daily) for 2 weeks. 2. In animals of both sexes, the pituitary-implanted and estradiol-treated rats had elevated plasma prolactin levels and had increased levels of striatal dopamine receptors. 3. We next investigated the possibility of an indirect action of estradiol via prolactin using hypophysectomized female rats (hypox) treated with 17 beta-estradiol or ovine prolactin (500 micrograms, twice daily) for 5 days. 4. Striatal dopamine receptor concentration was lower in hypox animals as compared to ovariectomized (85%, p less than 0.05) or intact female rats at random stage of the estrous cycle (76%, p less than 0.05) while the affinity (KD) of [3H]spiperone for these dopaminergic sites remained unchanged. 5. Treatment with estradiol or prolactin increased the level of striatal dopamine receptors (HYPOX + estradiol: 144% vs HYPOX, p less than 0.05; HYPOX + prolactin: 147% vs HYPOX, p less than 0.05). 6. These results indicate that high prolactin levels induced by pituitary implants or by injections of ovine prolactin lead, as observed with chronic estradiol treatment, to an increased density of striatal dopamine receptors. However, the effect of estradiol may not be explained exclusively by increased prolactin levels since the supersensitivity is also observed in hypophysectomized animals.

Dietary restriction retards the age-associated loss of rat striatal dopaminergic receptors.

In male Wistar rats subjected to dietary restriction by alternate days of feeding and fasting the normal age-associated loss of striatal dopamine receptors in the brain was substantially retarded. The mean survival time of the rats on the restricted diet was increased by approximately 40 percent compared to control rats given free access to food. Dopamine receptor concentrations in striata of 24-month-old rats that had been on a restricted diet since weaning were 50 percent higher than those of control animals of the same age, and essentially comparable to 3- and 6-month-old control rats.