Dopamine Receptors In Striatum Research Articles

Hints on the Lateralization of Dopamine Binding to D1 Receptors in Rat Striatum.

Dopamine receptors in striatum are important for healthy brain functioning and are the target of levodopa-based therapy in Parkinson's disease. Lateralization of dopaminergic neurotransmission in striata from different hemispheres occurs in patients, but also in healthy individuals. Our data show that the affinity of dopamine binding to dopamine D1 receptors is significantly higher in left than in right striatum. Analysis of data from radioligand binding to striatal samples from naïve, 6-hydroxydopamine lesioned, levodopa-treated and levodopa-induced dyskinetic rats shows differential receptor structure and gives hints on the causes of right/left lateralization of dopamine binding to striatal D1 receptors. Moreover, binding data showed loss of lateralization in levodopa (L-DOPA)-induced dyskinetic rats.

N-Methyl-d-aspartate (NMDA) Receptor Composition Modulates Dendritic Spine Morphology in Striatal Medium Spiny Neurons

Dendritic spines of medium spiny neurons represent an essential site of information processing between NMDA and dopamine receptors in striatum. Even if activation of NMDA receptors in the striatum has important implications for synaptic plasticity and disease states, the contribution of specific NMDA receptor subunits still remains to be elucidated. Here, we show that treatment of corticostriatal slices with NR2A antagonist NVP-AAM077 or with NR2A blocking peptide induces a significant increase of spine head width. Sustained treatment with D1 receptor agonist (SKF38393) leads to a significant decrease of NR2A-containing NMDA receptors and to a concomitant increase of spine head width. Interestingly, co-treatment of corticostriatal slices with NR2A antagonist (NVP-AAM077) and D1 receptor agonist augmented the increase of dendritic spine head width as obtained with SKF38393. Conversely, NR2B antagonist (ifenprodil) blocked any morphological effect induced by D1 activation. These results indicate that alteration of NMDA receptor composition at the corticostriatal synapse contributes not only to the clinical features of disease states such as experimental parkinsonism but leads also to a functional and morphological outcome in dendritic spines of medium spiny neurons.

Methylphenidate-evoked potentiation of extracellular dopamine in the brain of adolescents with premature birth: correlation with attentional deficit.

Perinatal anoxia/ischemia or premature birth increases the risk of developing attention deficit/hyperactivity disorder (ADHD). Brain imaging studies of idopathic ADHD reveal elevated dopamine transporter density in striatum of patients, predicting abnormal response to a challenge with methylphenidate in this population. We hypothesized that the severity of attention deficit in adolescents should correlate with the sensitivity to psychostimulant-evoked dopamine release. To test this hypothesis, we investigated six adolescent subjects (mean age 14.2 +/- 2.4 yr) with documented birth trauma and/or low birth weight and a diagnosis of ADHD. Using positron emission tomography (PET), we measured the relative binding of [(11)C]raclopride to dopamine receptors in striatum, first in the baseline condition and again after methylphenidate challenge at a therapeutic dose for ADHD (0.3 mg/kg, p.o.) in order to map the altered dopamine release evoked by the psychostimulant challenge. Neuropsychological measurements of impulsivity and inattention were also performed. We found a positive correlation between commission errors and the methylphenidate-evoked decrease in [(11)C]raclopride binding, thought to reflect the balance of dopamine release and reuptake. The greater the decline in the [(11)C]raclopride binding, the greater the ability of methylphenidate to block the reuptake of dopamine. As the ability to block the reuptake depends on the relative dopamine concentration, the result suggests that the impulsivity in these adolescents is associated with abnormally low extracellular dopamine concentration.

The involvement of dopamine in nociception: the role of D 1 and D 2 receptors in the dorsolateral striatum

Determination of the neuroanatomical and neurochemical factors that contribute to nociception is an essential element in the study and treatment of pain. Several lines of evidence have implicated nuclei and neurotransmitters within the basal ganglia in nociception. For example, previous studies have shown that dopamine receptors in the striatum are involved in acute nociception, however, it remains to be determined if dopamine receptors in the dorsolateral striatum are involved in persistent nociception. The purpose of the present study was therefore to determine whether activation or antagonism of dopamine receptors in the dorsolateral striatum influences the nociceptive responses of rats in the formalin test, a model of persistent pain. It was found that micro-injection of the non-selective dopamine antagonist haloperidol into the dorsolateral striatum increases formalin-induced nociception whereas injection of the non-selective dopamine agonist apomorphine reduces formalin-induced nociception. Injection of the D 1 antagonist SCH23390 or the D 1 agonist SKF38393 does not affect formalin-induced nociception. In contrast, injection of the D 2 antagonist eticlopride enhances formalin-induced nociception, whereas injection of the D 2 agonist quinpirole reduces formalin-induced nociception. These results provide additional evidence that dopamine receptors in the striatum are involved in nociception. Furthermore, this study strongly suggests that D 2, but not D 1, dopamine receptors in the dorsolateral striatum are involved in modulation of persistent nociception.

INTRASTRIATAL ADMINISTRATION OF AN OLIGODEOXYNUCLEOTIDE ANTISENSE TO THE D2 DOPAMINE RECEPTOR mRNA INHIBITS D2 DOPAMINE RECEPTOR-MEDIATED BEHAVIOR AND D2 DOPAMINE RECEPTORS IN NORMAL MICE AND IN MICE LESIONED WITH 6-HYDROXYDOPAMINE

Previous studies have shown that the intracerebroventricular injection of antisense oligodeoxynucleotides targeted to the mRNAs encoding the different subtypes of dopamine receptors inhibited behaviors mediated by these receptors. The present studies were designed to determine whether such antisense oligodeoxynucleotides could produce similar effects when injected into a discrete brain area. A D2 dopamine receptor antisense oligodeoxynucleotide (D2 antisense) was repeatedly injected into one corpus striatum of either normal mice or mice with unilateral lesions of the striatum induced by 6-hydroxydopamine. In the latter, intrastriatal injection of D2 antisense blocked the contralateral rotational behavior induced by the parenteral administration of the D2 dopamine receptor agonist quinpirole. The inhibitory effect of D2 antisense was dose- and time-related and was reversed upon cessation of D2 antisense treatment. This inhibitory effect was also selective in that D2 antisense treatment inhibited the rotational behavior induced by quinpirole but not that induced by the D1 dopamine receptor agonist SKF 38393 or by the muscarinic cholinergic agonist oxotremorine. Following repeated intrastriatal injections of D2 antisense into normal mice, parenteral administration of quinpirole caused rotational behavior ipsilateral to the side in which the D2 antisense was injected. No such rotational behavior was seen when similarly treated mice were challenged with SKF 38393 or oxotremorine. The quinpirole-induced rotational behavior in mice given intrastriatal injections of D2 antisense disappeared upon cessation of D2 antisense treatment. Repeated intrastriatal administration of D2 antisense also caused a significant reduction in the levels of D2, but not D1, dopamine receptors in striatum, as determined by receptor autoradiography. The levels of D2 dopamine receptors returned to normal upon cessation of D2 antisense treatment. Intrastriatal administration of an oligodeoxynucleotide with randomly placed nucleotides failed to alter the rotational response to quinpirole in either 6-hydroxydopamine-lesioned or normal mice and failed to alter the levels of D2 dopamine receptors in striatum. These results show that selective inhibition of behavioral responses mediated by D2 dopamine receptors can be achieved by the direct injection of a D2 antisense oligodeoxynucleotide into a discrete brain area. Copyright © 1996 Elsevier Science Ltd

Quantitative autoradiographic analysis of D 1 and D 2 dopamine receptors in rat brain in early and late pregnancy

This study examined the levels of D 1 and D 2 dopamine receptors in the rat brain during pregnancy, a physiologically unique and important naturally occurring state. We are particularly interested in changes in the dopamine receptor complement of the brain during pregnancy because these receptors might support some components of the immediate postpartum onset of normal maternal behavior. Quantitative in vitro receptor autoradiography was applied particularly focusing on brain areas that control maternal behavior. The D 1 dopamine receptor selective antagonist [ 3H]SCH23390 and the D 2 dopamine receptor selective antagonist [ 3H]spiperone were used as the ligands. We examined the levels of binding to D 1 and D 2 dopamine receptors in brains in females on day 2 (early pregnancy) and day 21 (late, but prepartum pregnancy) of pregnancy. In addition, brains from females on diestrus-1 and from males provided reference points to the existing literature. Late in pregnancy females had significantly 18–27% lower levels of binding to D 1 dopamine receptors in the lateral striatum, the medial striatum, and the nucleus accumbens when compared to all other groups. Late in pregnancy, females had also significantly 11–25% lower levels of binding to D 2 dopamine receptors in the lateral striatum, the anterior striatum, the nucleus accumbens and the olfactory tubercle compared to all other experimental groups. We examined all of the brain regions already established to be important for maternal behavior, and found that dopamine receptor binding changed across pregnancy only in one such region, the nucleus accumbens. Thus pregnancy, perhaps the hormones of pregnancy, reduces the levels of D 1 and D 2 dopamine receptors in the striatum, and the nucleus accumbens, but not in other brain regions.

Increases in striatal acetylcholine by SKF-38393 are mediated through D 1 dopamine receptors in striatum and not the frontal cortex

It has been proposed by some that the D 1 receptor effects are mediated through striatal actions while others have suggested that they are determined indirectly through the frontal cortex. The experiments reported here represent a further attempt to resolve this controversy. It was found that focal applications of the inactive and active enantiomers of SKF-38393 (a D 1 dopamine receptor agonist) to the rat striatum via reverse dialysis increased extracellular acetylcholine (ACh) in a stereoselective manner. Infusions of SKF-38393 into the frontal cortex, on the other hand, were ineffective in altering striatal ACh. Furthermore, partial hemisections caudal to the frontal cortex did not alter the ability of systemically administered SKF-38393 to increase striatal ACh. Taken together, these results suggest that at least some of the effects of D 1 receptor agonists on striatal cholinergic function are mediated through actions in the striatum and not the frontal cortex.

Differential pharmacological profile of striatal and cerebellar dopamine receptors labeled by [3H]quinpirole: identification of a discrete population of putative D3 receptors.

We have previously identified [3H]quinpirole-labeled dopamine receptors in the molecular layer of cerebellar lobule 10 which have a D2-like pharmacological profile, are guanine nucleotide-insensitive, and are juxtaposed to putative D3 receptor mRNA. This study compares the pharmacological profiles of [3H]quinpirole-labeled dopamine receptors in striatum and cerebellar lobule 10 using quantitative autoradiography. Dopaminergic compounds inhibited the specific binding of [3H]quinpirole in the caudate/putamen with the following rank order of potencies: spiperone > haloperidol > or = (+)butaclamol > or = quinpirole > or = 7-OH-DPAT > or = bromocriptine > clozapine > (-)sulpiride. In cerebellar lobule 10, a somewhat different rank order of potencies was observed: 7-OH-DPAT > quinpirole > or = bromocriptine > spiperone > (+)butaclamol > haloperidol > clozapine > (-)sulpiride. Quinpirole possessed equal affinity for [3H]quinpirole-labeled receptors in the caudate/putamen and cerebellum. 7-OH-DPAT exhibited 5-fold greater affinity for cerebellar receptors than those in the caudate/putamen. Spiperone, haloperidol, (+)butaclamol, and clozapine were more potent in competing for [3H]quinpirole binding at striatal dopamine receptors than cerebellar receptors by 83-, 59-, 11-, and 6-fold, respectively. The relative potencies of these compounds at striatal and cerebellar dopamine receptors are generally similar to the differential affinities reported at D2 and D3 dopamine receptors expressed in CHO cells, respectively. These data provide additional evidence that the dopamine receptors observed in cerebellar lobule 10 represent a discrete population of putative D3 receptors.

Effect of Repeated Treatment with Antidepressant Drugs and Electroconvulsive Shock (ECS) on the D2 Dopaminergic Receptor Turnover in the Rat Brain*

The effect of repeated treatment with citalopram, (+)oxaprotiline, (-)oxaprotiline, imipramine and ECS on the turnover of dopamine D2 receptors in the rat brain was measured using an N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-induced irreversible receptor inactivation method. Repeated treatment with citalopram and ECS, but not with (+) and (-) enantiomers of oxaprotiline and imipramine, significantly decreased the turnover of D2 receptors in the striatum. Neither of the applied repeated treatments changed the turnover of D2 receptors in the limbic system. The results suggest that changes in the turnover of D2 dopamine receptors in striatum may participate in the mechanism of antidepressant action of ECS and citalopram, but not that of (+) or (-)oxaprotiline or imipramine.

Increased uptake sites for serotonin and dopamine with decreased S2 serotonin receptors in microencephalic rat brain

Methylazoxymethanol (MAM)-induced cerebral hypoplasia resulted in a significant increase in densities of both serotonin uptake sites in frontal cortex and dopamine uptake sites in striatum, suggesting serotonergic and dopaminergic axons terminals were compressed in the smaller brain volumes. The density of S2 serotonin receptors in MAM-lesioned frontal cortex was decreased probably due to down-regulation, while densities of D1 and D2 dopamine receptors in striatum were identical between MAM-lesioned rats and control rats.

Chronic thioridazine treatment differently affects DA receptors in striatum and in mesolimbo-cortical systems

Chronic thioridazine administration (5 mg/kg for 22 days) caused both behavioral and dopamine (DA) receptor modifications in rats. After chronic thioridazine administration, a significant increase in both locomotion and stereotypies induced by apomorphine was observed. In particular, only sniffing increased significantly, whereas grooming behavior decreased and the number of rearings did not change. Autoradiographic data were consistent with the behavioral results. Chronic thioridazine caused an up-regulation of DA receptors both in the striatum and in the olfactory tubercle (O.T.). The striatal effect may account for the increase of stereotypies, whereas the effect in the olfactory tubercle may account for the increase in locomotion. An increase in DA receptors was also found in the medial (MCTX) and dorsal cortex (DCTX). However, a decrease in DA receptors appeared in the nucleus accumbens septi (NAS) and in the lateral cortex (LCTX). This decrease, selectively localized in the mesolimbic DA system, may represent the neurobiological substrate of the depolarization block observed in A10 neurons after chronic thioridazine treatment.

Responses of dopaminergic and serotonergic systems to triethyllead intoxication

Rats treated with triethyllead (TEL) exhibit a behavioral supersensitivity to challenge with dopamine agonists at 7 days following administration of TEL. In the present series of experiments, some neurochemical mechanisms which may affect this behavioral supersensitivity were detected. Administration of a single dose of TEL chloride (7.88 mg/kg, SC) to male Fischer-344 rats decreased the concentrations of dopamine in hippocampus, and of serotonin in olfactory tubercle, at Day 7 posttreatment. The ratio of 5-hydroxyindoleacetic acid/5-hydroxytryptamine (one estimate of serotonin turnover) was increased in nucleus accumbens ( p<0.05), with a similar trend in olfactory tubercle and striatum ( p<0.10). No changes were detected in binding of [ 3H]spiperone to D 2 dopamine receptors in striatum or olfactory tubercle. However, although basal adenylate cyclase activity was unaltered in TEL-treated rats, the V max for dopamine-stimulated adenylate cyclase activity was significantly elevated in olfactory tubercle. Conversely, TEL at micromolar concentrations markedly attenuated both basal and dopamine-stimulated adenylate cyclase activity in vitro in striatal homogenates. These data suggest the hypothesis that administration of TEL to rats results in an up-regulation of D 1 dopamine receptors in olfactory tubercle, and that the behavioral supersensitivity of TEL-treated animals to dopamine agonists may, in part, be a result of this receptor supersensitivity.

Modification of the function of D 1 and D 2 dopamine receptors in striatum and nucleus accumbens of rats chronically treated with haloperidol

With the aim of evaluating the possible functional modifications of both D 1 and D 2 dopamine receptor subpopulations after repeated administration of neuroleptics, the ability of selective D 1 and D 2 dopamine agonists to stimulate or inhibit, respectively, the activity of adenylate cyclase in the striatum and nucleus accumbens of rats treated with either saline or haloperidol for 21 days, was studied. It was found that stimulation of the activity of adenylate cyclase elicited by the selective D 1 receptor agonist SKF 38393 was significantly greater in homogenates of striatum in rats treated with haloperidol, than in those of saline-treated rats. Similarly, the inhibitory effect on the activity of the enzyme elicited by the selective D 2 agonist bromocriptine was much more evident in homogenates of the striatum from rats treated with neuroleptic than in those from saline-treated rats. When dopamine, sodium fluoride (NaF), or 5-guanylyl imidodiphosphate (Gpp(NH)p), were used as agonists to stimulate the activity of adenylate cyclase, the amount of cyclic AMP formed appeared the same in rats treated with haloperidol or saline. Dopamine receptors in nucleus accumbens behaved like those in the striatum in the pattern of modifications after repeated administration of haloperidol. Indeed, the inhibitory effect elicited by bromocriptine, as well as the stimulatory effect elicited by SKF 38393, was much more evident in nucleus accumbens from rats treated with haloperidol than in that from controls, whereas activation of adenylate cyclase induced by dopamine and sodium fluoride was similar in both experimental groups. Thus, the present results indicate that long-term treatment with haloperidol caused an up-regulation of both D 1 and D 2 subpopulations of dopamine receptors in striatum and nucleus accumbens of the rat.

Pharmacological characterization of binding sites identified in rat brain following in vivo administration of [3H]-spiperone.

[3H]-spiperone is commonly used to label dopamine receptors in vitro in brain tissue. However, spiperone also interacts with brain 5-hydroxytryptamine and noradrenaline receptors. In vivo, [3H]-spiperone has been used for identifying dopamine receptors in both animals and man but the nature of the sites identified is unknown. The in vivo administration of [3H]-spiperone to rats leads to a selective accumulation of radioactivity in the olfactory lobes, tuberculum olfactorium, nucleus accumbens, striatum, substantia nigra, hippocampus, frontal cortex and hypothalamus, when compared to the cerebellum. In vivo drug displacement studies suggest that the binding of [3H]-spiperone in these areas may be to dopamine, 5-HT or noradrenaline receptors. [3H]-spiperone in vivo mainly labels dopamine receptors in striatum, tuberculum olfactorium, hypothalamus, substantia nigra and olfactory lobes. However, in the frontal cortex and nucleus accumbens specific binding involves not only dopamine receptors but also 5-HT and/or noradrenaline receptors. Interpretation of in vivo studies in man using radioactive spiperone and its derivatives must take into account the fact that this ligand only labels dopamine receptors in some brain areas.

Characterization of D‐1 and D‐2 Dopamine Receptors in Striatum and Olfactory Tubercle

Characterization of D‐1 and D‐2 Dopamine Receptors in Striatum and Olfactory Tubercle

Suppression of L-dopa-induced circling in rats with nigral lesions by blockade of central dopa-decarboxylase: implications for mechanism of action of L-dopa in parkinsonism.

Dopamine (DA) elevations in rat striatum produced by combined administration of L-dopa and carbidopa were abolished when L-dopa was injected with NSD-1015, an inhibitor of central dopa-decarboxylase. In all rats with unilateral 6-OH-DA nigral lesions, L-dopa-induced contraversive circling occurred after carbidopa, but was totally abolished (in 60%) or markedly suppressed after pretreatment with NSD-1015. Administration of the DA metabolites DOPAC and HVA systemically and of 3-methoxytyramine intrastriatally evoked no circling in animals with 6-OH-DA lesions. In rats with unilateral nigrotomies, the direction of L-dopa-induced circling was reversed and became ipsiversive after DA receptors were reduced by the addition of kainic acid lesions in ipsilateral striata. Findings provide evidence that circling in rats--and by analogy, efficacy in parkinsonians--requires the decarboxylation of exogenous L-dopa and interaction of the formed DA with DA receptors in striatum.

Cyclo(Leu-Gly) has opposite effects on D-2 dopamine receptors in different brain areas

Cyclo(Leu-Gly) (cLG), a diketeopiprazine analog of Pro-Leu-Gly-NH 2 (MIF), affects a number of physiological and behavioral responses to the endogenous neurotransmitter, dopamine (DA). In the present series of experiments, the effect of in vivo administration of cLG (8 mg/kg) was investigated five days following subcutaneous administration. It was found that cLG administration caused a supersensitive behavioral response, measured by increased stereotypic sniffing, to the DA agonist, apomorphine (APO). At the same time, an increase was found in the affinity for dopamine (DA), as measured by dopamine inhibition of 3H-spiroperidol binding to D-2 DA receptors in striatum (nigro-striatal DA tract). In contrast, the same peptide treatment caused a subsensitive physiological response to APO-induced hypothermia, concomitant with a decrease in affinity for dopamine, as measured by DA inhibition of 3H-spiroperidol binding to D-2 DA receptors in hypothalamus (incerto-hypothalamic DA tract). These results suggest that a single neuromodulatory agent, the peptide cLG, can elicit diametrically opposite effects on D-2 DA receptors and on the corresponding physiological endpoints in two different brain areas.

Analogues of the neuroleptic agent isobutaclamol: Stereoisomeric 3b,4,5,6,7,9,9a,10-octahydro-[1]benzothiepino[2,3,4-ed]pyrido[2,1-a]isoquinolin-5-ols and some related compounds

10,11-Dihydrodibenzo[b,f]thiepin-10-carbonitrile (XVI) was reduced with aluminium hydride to the primary amine XVII which was formylated with acetic formic anhydride. The formamide derivative was cyclized by the Bischler-Napieralski reaction to the condensed dihydroisoquinoline XX. Addition of methyl vinyl ketone to the hydrochloride of compound XX at 100 °C gave a mixture of the stereoisomeric 3b,4,5,6,7,9,9a,10-octahydro[1]benzothiepino[2,3,4-ed]pyrido[2,1-a]isoquinolin-5-ones (XIII) which was separated by chromatography to the major 3b,9a-cis isomer XIIIb and the minor 3b,9a-trans isomer XIIIa to which the configuration was assigned on the basis of analogy. Reactions of both ketones with tert-butylmagnesium chloride and isopropyllithium led to mixtures whose chromatographic separation afforded the tertiary alcohols XIa, XIb, XIIa and XIIb mostly in low yields. In most cases the main products were the secondary alcohols XIV and apparently also the pinacols XXIII, formed by reduction. An attempt at preparing similar [1]benzothiopyrano[2,3,4-ed]pyrido[1,2-a]isoquinoline derivatives was discontinued because of an anomalous result of cyclization of compound XXVII. Compound XIa, being a 15-thia analogue of isobutaclamol (VI) displayed a high affinity to dopamine receptors in striatum of the rat brain which confirms the correctness of the assignment of relative configuration on C(3b) and C(9a).

The effect of melanotropin release inhibiting factor, its metabolites and analogs on [ 3H]spiroperidol and [ 3H]apomorphine binding sites

1. 1. The effects of melanotrophin release inhibiting factor (Pro-Leu-Gly-NH 2, MIF), its possible metabolites, Pro-Leu-OH, Leu-Gly-NH 2, Leu-Gly-OH and an analogue, cyclo(Leu-Gly), on [ 3H]spiroperidol binding sites in the striatum and on [ 3H]apomorphine binding sites in the striatum and hypothalamus of male Sprague-Dawley rats were determined. 2. 2. [ 3H]Spiroperidol binding to dopamine receptors in striatal membranes was unaffected by any of the above peptides in concentration up to 0.1 mM. 3. 3. The binding of [ 3H]apomorphine was enhanced by MIF, Pro-Leu-OH and cyclo(Leu-Gly) in both striatal and hypothalamic membranes in submicromolar concentrations. Leu-Gly-NH 2 and Leu-Gly-OH did not affect [ 3H]apomorphine binding to dopamine receptors in striatum of hypothalamus. 4. 4. The enhancement in binding of [ 3H]apomorphine by MIF and cyclo(Leu-Gly) was not related to the changes in the number of binding sites but to an increase in the affinity to the receptors. 5. 5. The results indicate that MIF and some of its related peptides do not affect dopamine receptor binding sites labeled by the neuroleptic [ 3H]spiroperidol but facilitate the transmission in those sites labeled by [ 3H]apomorphine. Since [ 3H]apomorphine and [ 3H]spiroperidol predominantly label pre- and post-synaptic dopamine receptors, it is concluded that MIF and its active analogs interact with presynaptic dopamine receptors.

Competition by estrogens for catecholamine receptor binding in vitro.

We have examined the ability of various steroids to compete for high-affinity binding of 3H-labeled ligands to catecholamine receptors in membranes prepared from rat cerebral cortex, striatum, and anterior pituitary. Ligands employed were: [3H]WB4101, [3H]prazosin, [3H]yohimbine, and [3H]clonidine (alpha-noradrenergic); [3H]dihydroalprenolol (beta-noradrenergic); [3H]spiperone and [3H]ADTN (dopaminergic). Only the 17 beta estrogens were effective and only binding of [3H]spiperone and [3H]ADTN in striatum and [3H]WB4101 and [3H]prazosin in cerebral cortex was reduced. Thus putative dopaminergic and alpha 1-noradrenergic sites alone appear to recognize estrogens. A slight competitive effect on [3H]spiperone binding to anterior pituitary membranes was also observed. Among the 17 beta estrogens tested, the most effective in all cases was the catechol estrogen 2-hydroxyestradiol (2-OHE2). The ability of 2-OHE2 (IC50 = 20-30 micro M) to inhibit ligand binding to alpha 1 receptors was comparable to that of norepinephrine (IC50 = 10-20 micro M), whereas for dopamine receptors in striatum and pituitary 2-OHE2 was an order of magnitude less effective than dopamine (IC50 = 12 micro M) in reducing binding of 3H ligands. Estradiol-17 beta and 2-hydroxyestrone were also able to inhibit binding, but the order of steroid potency was different for alpha 1 and dopaminergic receptors. Progesterone, testosterone, and corticosterone were without effect in all cases. These results show that there is specificity of steroid interactions with catecholamine receptors in the brain, both in terms of steroid structure and receptor type. The possible relevance of these interactions to neuroendocrine function is discussed.