Prefrontal,accumbal [shell] and ventral striatal mechanisms in jaw movements and non-cyclase-coupled dopamine D1-like receptors

The effect on jaw movements of intracerebral injections of the dopamine D1-like receptor agents SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), SK&F 38393 ([R]-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and of injections of the dopamine D2-like receptor agonist quinpirole into the ventrolateral striatum, accumbens shell or prefrontal cortex were studied. SK&F 38393 and SK&F 83959 injected into the ventrolateral striatum synergised with i.v. quinpirole; in the shell of accumbens, SK&F 38393 evidenced weaker synergism with quinpirole, while SK&F 83959 did not synergise with it; neither agent synergised with quinpirole in the prefrontal cortex. Co-injection of SCH 23390 or SK&F 83959 into the prefrontal cortex antagonised jaw movements induced by injection of SK&F 83959 into the ventrolateral striatum in combination with i.v. quinpirole. Injection of SK&F 83959 + quinpirole into the ventrolateral striatum, but not into the accumbens shell, resulted in synergism. These findings indicate a primary, but not exclusive, role for ventral striatal, non-cyclase-coupled dopamine D1-like receptors in the induction of jaw movements. These processes appear to require tonic activity of prefrontal cyclase-linked dopamine D1A [and/or D1B] receptors.     

SK&F 83959 and non-cyclase-coupled dopamine D1-like receptors in jaw movements via dopamine D1-like/D2-like receptor synergism

This study compared the effects of the dopamine D1-like receptor agents SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro- 1 H-3-benzazepine), which inhibits the stimulation of adenylyl cyclase, and A 68930 ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenyl-isochroman), a full efficacy agonist, in regulating jaw movements in the rat by synergism with dopamine D2-like receptor agonism. When SK&F 83959 and A 68930 were given in combination with quinpirole, there was a synergistic induction of jaw movements. Responsivity to SK&F 83959 + quinpirole was antagonised by the dopamine D1-like receptor antagonists SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-ben zaz epine) and BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7-hydroxy-2-methyl- 1,2,3,4-tetrahydroisoquinoline); synergism was antagonised also by the dopamine D2-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-++ +methyl-aminobenzamide). Responsivity to A 68930 + quinpirole was enhanced by low doses of SCH 23390, BW 737C and YM 09151-2, and antagonised by higher doses of SCH 23390 and YM 09151-2. These results implicate a novel, dopamine D1-like receptor that is coupled to a transduction system other than/additional to adenylyl cyclase, and suggest that its functional role extends to the regulation of jaw movements by synergistic interactions with dopamine D2-like receptors.     

Topographical resolution of jaw movements mediated by cyclase- vs. non-cyclase-coupled dopamine D(1)-like receptors: studies with SK&F 83822

This study examined the effects on orofacial movement topography of SK&F 83822 ([R/S]-6-chloro-7,8-dihydroxy-3-allyl-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), which stimulates dopamine D(1)-like receptors coupled to stimulation of adenylyl cyclase (AC) but not phosphoinositide (PI) hydrolysis, in comparison with SK&F 83959 ([R/S]-3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), which stimulates PI hydrolysis but not AC. SK&F 83822 alone induced chattering, while SK&F 83959 alone exerted little effect. SK&F 83822 and SK&F 83959 each in combination with the dopamine D(2)-like agonist quinpirole resulted in synergistic induction of non-chattering movements with tongue protrusions. These effects were blocked by the dopamine D(1)-like receptor antagonist SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine). However, the dopamine D(2)-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide) exerted a biphasic effect on synergism with SK&F 83822: chattering was initially released but antagonised thereafter. Only antagonism was seen for synergism with SK&F 83959. While both AC- and PI-coupled dopamine D(1)-like receptors participate in synergistic dopamine D(1)-like:D(2)-like receptor interactions, topographically specific synergistic and oppositional dopamine D(1)-like:D(2)-like interactions evident with SK&F 83822 reflect the involvement primarily of D(1)-like receptors coupled to AC rather than PI.     

Functional interaction between dopamine D1 and D2 receptors in rat jaw movements.

The functional interaction between dopamine D1 and D2 receptors in dopamine-mediated jaw movements was studied in ketamine-anaesthetized rats after C1 spinal transection. Jaw movements were recorded by means of a light-emitting diode attached to the mandible; the method permits a detailed qualitative and quantitative analysis of jaw movements. D1 stimulation with SKF38393 (10 mg/kg i.v.) produced frequent bursts of teeth chattering, which were abolished by pretreatment with SCH23390 (0.25 mg/kg i.v.). D2 stimulation by quinpirole (1-10 mg/kg i.v.) produced infrequent bursts of jaw movements, which were characterized by low frequency jaw opening and closure movements from the rest position of the jaw, and absence of tongue protrusions. An additional stimulation of D1 receptors by giving SKF38393 30 min later produced an almost continuous pattern of jaw openings but less closure movements from the rest position, and the openings were accompanied by frequent tongue protrusions. These results clearly demonstrate that the type of oral behaviour produced by stimulation of D1 and D2 receptors together is qualitatively different from that produced by stimulation of either D1 or D2 receptors alone.     

Topographical assessment and pharmacological characterization of orofacial movements in mice: dopamine D(1)-like vs. D(2)-like receptor regulation

A novel procedure for the assessment of orofacial movement topographies in mice was used to study, for the first time, the individual and interactive involvement of dopamine D(1)-like vs. D(2)-like receptors in their regulation. The dopamine D(1)-like receptor agonists A 68930 ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenyl-isochroman) and SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine) each induced vertical jaw movements with tongue protrusions and incisor chattering. The dopamine D(1)-like receptor antagonists SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) antagonised these responses, while the dopamine D(2)-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide) attenuated those to SK&F 83959 and released horizontal jaw movements. These findings suggest some role for a dopamine D(1)-like receptor that is coupled to a transduction system other than/additional to adenylyl cyclase, and for dopamine D(1)-like:D(2)-like receptor interactions, in the regulation of individual orofacial movement topographies in the mouse. This methodology will allow the use of knockout mice to clarify the roles of individual dopamine receptor subtypes in their regulation.     

Long-term effects of postnatal amphetamine treatment on striatal protein kinase A activity, dopamine D(1)-like and D(2)-like binding sites, and dopamine content

The purpose of the present study was to determine whether exposure to amphetamine during the preweanling period would alter dopaminergic functioning in the dorsal striatum of adult rats. In three experiments, we assessed the effects of repeated amphetamine treatment on striatal protein kinase A (PKA) activity, dopamine (DA) D₁-like and D₂-like binding sites, and DA content. Rats were pretreated with saline or amphetamine (2.5 mg/kg, ip) for 7 consecutive days starting on postnatal day (PD) 11. At PD 90, rats were killed and their dorsal striata (i.e., caudate–putamen) were removed and frozen until time of assay. Amphetamine pretreatment produced long-term reductions in both striatal PKA activity and DA content. Early amphetamine exposure also resulted in an upregulation of D₂-like binding sites, while leaving D₁-like binding sites unaffected. It is likely that the upregulation of D₂-like binding sites was stimulated by the persistent decline in striatal DA levels. Although speculative, it is possible that excess striatal D₂-like receptors were responsible for inhibiting PKA activity through actions on the cAMP signal transduction pathway. The behavioral relevance of these amphetamine-induced neurochemical changes has not yet be determined.     

Saturation of striatal D(2) dopamine receptors by clozapine

Positron emission tomography (PET) studies have demonstrated low striatal D2 dopamine receptor occupancy in clozapine-treated schizophrenic patients. The aim of this pilot study was to explore if this low receptor occupancy indeed represents partial saturability of striatal D2 dopamine receptors by clozapine. Three anaesthetized Cynomolgus monkeys were examined during one day with PET and [11C]raclopride at baseline and after intravenous injections of clozapine 1.5 mg/kg followed by 18.5 mg/kg. The estimated corresponding human oral doses were approx. 210 mg/d and 2800 mg/d. D2 dopamine receptor occupancy was calculated using an equilibrium-ratio analysis and ranged from 54 to 58% after 1.5 mg/kg and 87 to 89% after the total dose 20 mg/kg. The calculated maximal occupancy was 93%. We conclude that PET-measured D2 dopamine receptor occupancy by clozapine can be described using a model based on the law of mass action, previously validated for conventional antipsychotics. Therefore, sufficiently high doses of clozapine are expected to produce complete striatal D2 dopamine receptor occupancy. The findings further support our previous findings of low D2 dopamine receptor occupancy in patients treated with standard doses of clozapine.     

Striatal dopamine D1-like receptors have higher affinity for dopamine in ethanol-treated rats.

Experiments were carried out with brain tissues of ethanol-experienced (long-term ethanol intake but withdrawn) vs. ethanol-naive animals. The in vitro 3H antagonist binding of [3H]SCH 23390 and of [3H]spiperone to striatal dopamine D1- and D2-like receptors revealed no significant changes in KD and Bmax values. Displacement of the 3H antagonist binding by dopamine indicated high- and low-affinity states, which also showed no significant alteration at the D2-like receptor but a 5-fold increase of dopamine affinity at the high-affinity state of the D1-like receptor of the ethanol-experienced rats.     

The dopamine agonism on ADP-stimulated platelets is mediated through D2-like but not D1-like dopamine receptors

Monoamines such as serotonin and epinephrine are known to be involved in platelet activation and aggregation. Dopamine is another monoamine identified in platelets, but published data about its effect on platelets and the receptors involved are controversial. In the present study, we investigated the dopamine agonism in platelets and the receptors involved in these pathways. Platelet-rich plasma (PRP) of healthy individuals was treated with agonists (ADP, epinephrine, dopamine) and various dopamine receptor and transporter antagonists such as SCH-23390, raclopride, clozapine, methylphenidate, and cocaine. Platelet activation was investigated by flow cytometry (CD62P and CD63 surface expression), optical aggregometry, and microaggregate adhesion to collagen IV in a flow chamber system. In our study, dopamine on its own had no effect on platelet activation in the different assays. However, when used in combination with ADP (10 μM), dopamine in a range of 1 to 100 μM significantly potentiated platelet microaggregate formation and adhesion to collagen under low shear flow conditions. Specific antagonists for D2-like receptors (L-741,626, raclopride, and clozapine) completely diminished the dopamine effect at selective concentrations, but not the effect of epinephrine. Neither the D1-like receptor antagonist SCH-23390 nor dopamine transporter antagonists (methylphenidate, cocaine) showed inhibitory effects on the dopamine agonism. Thus, dopamine is an ADP-dependent platelet agonist which acts via D2-like but not D1-like receptors or adrenergic receptors. Because many psychopharmacological drugs are directed to D2-like receptors, platelet dysfunction in patients being treated with such drugs may be linked to these mechanisms.     

Modification of dopamine D(1) receptor knockout phenotype in mice lacking both dopamine D(1) and D(3) receptors

Experimental evidence suggests that dopamine D(1) and D(3) receptors may interact in an opposing or synergistic fashion. To investigate interactions between both receptors in behaviour, we have used dopamine D(1) and D(3) receptor knockout mice to generate mice lacking both receptors. D(1)(-/-)D(3)(-/-) mice were viable, fertile and showed no gross morphological abnormalities. In an open field, they exhibited lower activity than wild-type, D(1)(-/-) and D(3)(-/-) mice. D(1)(-/-)D(3)(-/-) mice performed equally poorly in the rotarod and Morris water maze tasks as their D(1)(-/-) littermates. Basal locomotor activity and anxiety-like behaviour were normal in D(1)(-/-)D(3)(-/-) mice. Combined deletion of both receptors abolished the exploratory hyperactivity and anxiolytic-like behaviour of dopamine D(3) receptor mutant phenotype and further attenuated the low exploratory phenotype of D(1)(-/-) mice. These results imply an interaction of both receptors in the expression of exploratory behaviour in a novel environment, and the need for the presence of intact dopamine D(1) receptor for the expression of certain behaviours manifested in dopamine D(3) receptor mutant phenotype. In addition, dopamine D(1) receptor, but not dopamine D(3) receptor, is involved in the ability to perform on the rotarod and spatial learning.     

High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia

The 'atypicality' of the antipsychotic drug, amisulpride, has been attributed to preferential extrastriatal binding. Previous investigations of striatal D2 receptor occupancy by amisulpride revealed conflicting results. The aim of this PET study was to measure the striatal occupancy by amisulpride and to correlate it with the corresponding drug plasma concentrations. Nine amisulpride-treated patients and 12 healthy volunteers serving as controls were studied with PET and [18F]desmethoxyfallypride. Occupancy values and plasma concentrations were nonlinearly fitted to an E max model. Results showed 43-85% (putamen) and 67-90% (caudate) D2-like receptor occupancy. Plasma amisulpride concentrations at the time of tracer injection, but not administered doses, were significantly nonlinearly correlated to occupancy levels (putamen: rS=0.88, p=0.0017; caudate: r S=0.78, p=0.0127). Calculated Emax was similar in both caudate and putamen, but occupancy levels were lower in caudate at lower amisulpride plasma concentrations. Calculated plasma levels to attain 60-80% receptor occupancy ranged from 119 to 474 ng/ml (caudate) and from 241 to 732 ng/ml (putamen). This reveals a broad range of plasma concentrations producing less than 80% striatal receptor occupancy. However, our data show high striatal D2-like receptor occupancies under rising plasma concentrations. Using the full range of recommended amisulpride dosage, striatal occupancies up to 90% can be measured.     

Effect of chronic nicotine treatment and withdrawal on rat striatal D1 and D2 dopamine receptors.

The effects on rat striatal dopamine receptors after chronic nicotine administration (3 and 12 mg kg-1 day-1), and after withdrawal from chronic nicotine (12 mg kg-1 day-1), were studied. After 21 days of continuous minipump infusion, the control (saline) and nicotine-treated rats were killed. The nicotine-withdrawal rats were killed on day 28, 7 days after pump removal. Radioligand studies were performed to determine D1 ([3H]SCH23390) and D2 ([3H]spiperone) striatal dopamine receptor affinity (Kd) and maximum binding (Bmax). Dopamine inhibition of antagonist binding at 3 concentrations and the effect of 0.3 mM GTP on binding affinity were examined. No statistically significant differences between control and nicotine treatment or withdrawal groups were noted in either D1 or D2 receptor Kd or Bmax. Although nicotine has been shown to affect nigrostriatal dopamine release, chronic treatment does not appear to alter overall striatal dopaminergic receptor binding parameters.     

Differential role of dopamine D1 and D2 receptors in isoniazid-induced vacuous chewing movements

Tardive dyskinesia (TD) is a syndrome of potentially irreversible and involuntary hyperkinetic disorders that occurs during chronic neuroleptic therapy and is a major limitation of such therapy. Vacuous chewing movements (VCMs) in rats have been widely accepted as an animal model of tardive dyskinesia. In the present study isoniazid (1, 2 and 5 microM i.c.v.) dose-dependently produced VCMs in rats. The response produced by a 10-microM dose was lower than that of earlier doses but was statistically significant when compared to a saline-treated group. Diazepam (1 and 4 mg/kg i.p.) and progabide (50 and 100 mg/kg i.p.) dose-dependently reversed the isoniazid-induced VCMs. Haloperidol (0.5 and 1 mg/kg i.p.) and SCH-23390 (0.25 and 0.5 mg/kg i.p.) reversed the isoniazid-induced VCMs in a dose-dependent manner. Sulpiride (25 and 50 mg/kg i.p.), a dopamine D2 receptor antagonist, had no effect on isoniazid-induced VCMs. SKF-38393 (10 and 15 mg/kg i.p.) dose-dependently augmented the isoniazid-induced VCMs. Quinpirole 0.02 mg/kg i.p. had no effect on isoniazid-induced VCMs but a higher quinpirole dose (0.05 mg/kg) significantly reduced isoniazid-induced VCMs. Isoniazid (2 microM i.c.v.) produced stereotypy (grooming and rearing) in rats. Haloperidol (0.5 and 1 mg/kg i.p.), SCH-23390 (0.25 and 0.5 mg/kg i.p.) and sulpiride (25 and 50 mg/kg i.p.) decreased the severity of isoniazid-induced stereotypy. SKF-38393 (10 and 15 mg/kg i.p.) dose-dependently augmented the isoniazid-induced grooming behavior more prominently as compared to quinpirole (0.02 and 0.05 mg/kg i.p.); on the other hand quinpirole potentiated isoniazid-induced rearing behavior. In conclusion, the results of the present study demonstrated the differential involvement of dopamine D1 and D2 receptors in isoniazid-induced VCMs.     

Psychostimulant sensitization: differential changes in accumbal shell and core dopamine

The nucleus accumbens has been subdivided into a shell and a core compartment on the basis of histochemical and connectional differences. Recently, we reported that behavioral sensitization to morphine is associated with an increased dopamine transmission in the caudate-putamen and in the nucleus accumbens core as well as a decreased response in the nucleus accumbens shell following acute morphine challenge. We have now performed a similar study in rats sensitized to amphetamine and to cocaine. Behavioral sensitization was induced by daily administration of a single dose of 1 mg/kg s.c. of amphetamine for 10 days or of 10 mg/kg i.p. of cocaine twice a day for 14 days. Microdialysis was performed 10-14 days after the last injection of amphetamine and 7-10 days after the last injection of cocaine. Both schedules resulted in robust behavioral sensitization in response to challenge with 0.25 and 0.5 mg/kg of amphetamine and to 5 and 10 mg/kg of cocaine, respectively. Subjects pre-exposed to amphetamine showed a sensitization of dopamine transmission in the nucleus accumbens core but not in the nucleus accumbens shell. Subjects pre-exposed to cocaine showed sensitization of dopamine transmission in the core only to the lower dose of cocaine. In the shell no change was observed after the lower dose of cocaine while a significant reduction of the dopamine response was observed after the higher dose. These results suggest that behavioral sensitization might result from reciprocal changes in the response of nucleus accumbens dopamine in the shell and in the core to drug challenge.     

Evidence that the enhancement of dopamine function by repeated electroconvulsive shock requires concomitant activation of D1-like and D2-like dopamine receptors

In this study, the behavioural response to dopamine D₁-like receptor agonists (SKF 38393, SKF 81297 and SKF 77434) and D₂-like receptor agonists (quinpirole and RU 24213), administered alone and in combination to rats treated repeatedly with electroconvulsive shock (five ECS over 10 days) or sham, was tested. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Repeated ECS (compared to sham controls) had no significant effect on the behavioural response to SKF 38393 (7.5 mg/kg SC), SKF 81297 (0.2 mg/kg SC), SKF 77434 (0.1 mg/kg SC), quinpirole (0.1 and 0.25 mg/kg SC) or RU 24213 (0.3 mg/kg SC), when administered alone. In contrast, repeated ECS markedly increased locomotion (activity counts and scores) induced by the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) and by co-administration of a D₁-like agonist plus a D₂-like agonist [SKF 38393 (7.5 mg/kg SC) plus quinpirole (0.25 mg/kg SC), SKF 81297 (0.2 mg/kg SC) plus quinpirole (0.1 mg/kg SC), and SKF 77434 (0.1 mg/ kg SC) plus RU 24213 (0.3 mg/kg SC)]. This ECS-induced enhancement of dopamine-mediated behaviour was observed for up to 3 weeks after cessation of ECS treatment. In addition, ECS also enhanced the locomotor response to intra-accumbens SKF 38393 plus quinpirole (0.4 and 1.0 μg/side, respectively). These results provide evidence that the enhancement of dopamine function by repeated ECS requires concomitant stimulation of both D₁-like and D₂-like receptors, and that this effect is long-lasting. Received: 24 January 1997 /Final version: 5 March 1997     

Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D1-like receptors in neonatal rats

BACKGROUND AND PURPOSE

Dopamine released from the endings of descending dopaminergic nerve fibres in the spinal cord may be involved in modulating functions such as locomotion and nociception. Here, we examined the effects of dopamine on spinal synaptic transmissions in rats.

EXPERIMENTAL APPROACH

Spinal reflex potentials, monosynaptic reflex potential (MSR) and slow ventral root potential (sVRP), were measured in the isolated spinal cord of the neonatal rat. Dopamine release was measured by HPLC.

KEY RESULTS

Dopamine at lower concentrations (<1 µM) depressed sVRP, which is a C fibre-evoked polysynaptic response and believed to reflect nociceptive transmission. At higher concentrations (>1 µM), in addition to a potent sVRP depression, dopamine depolarized baseline potential and slightly depressed MSR. Depression of sVRP by dopamine was partially reversed by dopamine D₁-like but not by D₂-like receptor antagonists. {"type":"entrez-protein","attrs":{"text":"SKF83959","term_id":"1155968032","term_text":"SKF83959"}}SKF83959 and {"type":"entrez-protein","attrs":{"text":"SKF81297","term_id":"1156277425","term_text":"SKF81297"}}SKF81297, D₁-like receptor agonists, and methamphetamine, an endogenous dopamine releaser, also caused the inhibition of sVRP. Methamphetamine also depressed MSR, which was inhibited by ketanserin, a 5-HT_2A/2C receptor antagonist. Methamphetamine induced the release of dopamine and 5-HT from spinal cords, indicating that the release of endogenous dopamine and 5-HT depresses sVRP and MSR respectively.

CONCLUSION AND IMPLICATIONS

These results suggested that dopamine at lower concentrations preferentially inhibited sVRP, which is mediated via dopamine D₁-like and other unidentified receptors. The dopamine-evoked depression is involved in modulating the spinal functions by the descending dopaminergic pathways.     

Relative roles of ventral striatal D1 and D2 dopamine receptors in responding with conditioned reinforcement

Several experiments investigated the involvement of D₁ and D₂ dopamine receptors in the ventral striatum in the control over behaviour by a conditioned reinforcer using an acquisition of new response procedure. Intra-accumbens infusion of either the D₁ receptor antagonist, SCH 23390, or the D₂ receptor antagonist, raclopride, completely blocked the potentiative effects of intra-accumbensd-amphetamine on responding with conditioned reinforcement and reduced responding to control levels. SCH 23390 was more potent than raclopride. At higher doses in the absence ofd-amphetamine, both antagonists also blocked the preference for responding on the lever producing the conditioned reinforcer. Intra-accumbens infusions of either the D₁ receptor agonist, SKF 38393, or the D_2/3 receptor agonist, LY 171555 (quinpirole), selectively potentiated responding on the lever producing the conditioned reinforcer. Various combined infusions of the D₁ and D₂ agonists in specific low doses had additive, but not synergistic, effects on responding with conditioned reinforcement. None of the drugs affected the drinking of water in deprived subjects when infused intra-accumbens. These results suggest that both D₁ and D₂ receptors in the nucleus accumbens are involved in mediating the effects of dopamine in potentiating the control over behaviour by conditioned reinforcers.     

BHT-920 and LY-171555 (quinpirole) have similar affinities for striatal D-2 dopamine receptors, and similar affinities for striatal D-1 dopamine receptors

The affinity of LY-171555 (quinpirole) and BHT-920 for both states of rat striatal dopamine D-1 and D-2 receptors was determined. Although these drugs have different pharmacological effects in experimental animals, we found that they had similar affinities for both D-1 and D-2 receptors.