Role Of Dopamine D1 Receptors Research Articles

Loss of Alternative Non-Drug Reinforcement Induces Relapse of Cocaine-Seeking in Rats: Role of Dopamine D1 Receptors

Animal models of relapse to drug seeking have focused primarily on relapse induced by exposure to drugs, drug-associated cues or contexts, and foot-shock stress. However, relapse in human drug abusers is often precipitated by loss of alternative non-drug reinforcement. The present experiment used a novel 'resurgence' paradigm to examine relapse to cocaine seeking of rats as a result of loss of an alternative source of non-drug reinforcement. Rats were first trained to press a lever for intravenous infusions of cocaine. Next, cocaine deliveries were omitted and food pellets were provided for an alternative nose-poke response. Once cocaine seeking was reduced to low levels, food pellets for the alternative response were also omitted. Cocaine seeking increased with the loss of the alternative non-drug reinforcer (ie, resurgence occurred) despite continued extinction conditions. The increase in cocaine seeking did not occur in another group of rats injected with SCH 23390 before the loss of the alternative reinforcer. These results suggest that removal of an alternative source of reinforcement may induce relapse of cocaine seeking and that the dopamine D(1) receptor may have a role in this effect.

In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5

Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of pituitary adenomas. Medical therapy with somatostatin analogues (SSAs) effectively reduces TSH secretion in approximately 80% of patients and induces shrinkage in about 45% of tumors. According with previous data, resistance to SSA treatment might be due to heterogeneity in somatostatin receptors (SSTRs) expression. We report the case of TSHoma in a 41-year-old man treated with octreotide LAR that caused a dramatic decrease of TSH and thyroid hormones and tumor shrinkage already after 3 months of pre-surgical therapy. In search of potential molecular determinants of octreotide effectiveness, we measured, in primary cultures from this tumor, SSTR and dopamine D2 receptor (D2R) expression, and octreotide and/or cabergoline effects on TSH secretion and cell proliferation. SSTR5 and D2R expression was higher than SSTR2. Octreotide significantly inhibited TSH secretion more effectively than cabergoline (P<0.001), whereas the combined treatment was comparable with cabergoline alone. Similarly, octreotide resulted more effective than cabergoline on cell proliferation, while the combination did not show any additive or synergistic effects. In conclusion, the significant antisecretive and antiproliferative effect of octreotide in this patient might be related to the high expression of SSTR5, in the presence of SSTR2. After reviewing the literature, indeed, in line with previous observations, we hypothesize that SSTR5/SSTR2 ratio in TSHomas may represent a useful marker in predicting the outcome of therapy with SSAs. The role of D2R should be further explored considering that the presence of D2R can influence SSTRs functionality.

Role of Dopamine D1 Receptors in the Activation of Nucleus Accumbens Extracellular Signal-Regulated Kinase (ERK) by Cocaine-Paired Contextual Cues

Exposure to drug-paired cues can trigger addicts to relapse into drug seeking. Although the molecular mechanisms underlying cue-elicited cocaine seeking are incompletely understood, the protein kinase extracellular signal-regulated kinase (ERK) is known to have an important role. Psychostimulants and their associated cues can activate ERK in medium spiny neurons of the nucleus accumbens core (AcbC). These medium spiny neurons can be classified according to their projections (to ventral pallidum and/or substantia nigra) and by their mRNA expression. The present experiments were designed to determine which distinct set of AcbC projection neurons expresses phosphorylated ERK (pERK) in response to cocaine-paired contextual cues. Combined use of the retrograde label Flurogold with immunohistochemical staining of pERK was used to show that the AcbC pERK accompanying preference for cocaine-paired contexts occurs in both the accumbens (Acb)-nigral and Acb-pallidal projections. The gene expression characteristics of the neurons expressing pERK in response to cocaine-paired cues was further investigated using combined in situ hybridization and immunocytochemistry to show that AcbC pERK+ cells correspond to D1, but not preproenkephalin, mRNA+ cells. Furthermore, intra-AcbC infusion of the D1-antagonist SCH23390 attenuated cue-induced AcbC pERK expression. In aggregate, these results indicate that (i) the D1-expressing AcbC neurons evidence long-term plasticity related to drug-cue memories and (ii) local dopamine D1 receptors are necessary for the expression of cocaine-paired cue-induced pERK in these AcbC neurons.

Dopamine D3 receptor knock-out mice display deficits in locomotor sensitization after chronic morphine administration

Locomotor sensitization is the progressive and enduring enhancement of locomotion induced by stimulants such as drugs, which alter rodent locomotion in a long-standing manner. The dopamine D3 receptor has been reported to play a role in morphine addiction. The aim of the present study was to investigate the role of dopamine D3 receptor in the morphine induced locomotor sensitization using dopamine D3 receptor knock-out mice. The dopamine D3 receptor knock-out mice did not display an enhanced behavioral response to acute morphine administration or develop an increased rate of locomotor sensitization to intermittent morphine administration. When 2 mg/kg naloxone was co-administered with 10 mg/kg morphine, morphine-induced locomotion sensitization in wild-type mice was significantly blocked while the locomotion in the D3 receptor knock-out mice was decreased. Then the wild-type mice were administered with dopamine D3 antagonist nafadotride. It was found that co-administration of morphine with nafadotride could effectively suppress the level of morphine induced behavioral sensitization. It was concluded that a loss of the dopamine D3 receptor gene may inhibit acute morphine induced hyperlocomotor activity and chronic morphine induced behavioral sensitization.

Dopamine D3 receptor regulates basal but not amphetamine-induced changes in pain sensitivity in mice

Pain is a complex and subjective experience that involves not only the transduction of noxious stimuli by nociceptive fibers, but also the cognitive and emotional processing by the brain. Previous studies on the transmission of nociception suggest that the activation of mesolimbic dopamine (DA) system plays an important role in mediating the suppression of tonic pain. The aim of the current study was to examine the role of DA D3 receptor in modulating basal and amphetamine-induced changes in pain sensitivity in mice. We used wild-type and D3 receptor mutant mice and determined allodynia induced by both noxious heat (radiant heat) and mechanical (von Frey hair) stimuli. We show that D3 receptor mutant mice exhibit hypoalgesia in both the tail-flick test and von Frey hair test compared to wild-type mice. Amphetamine-induced hyperalgesia in both D3 receptor mutant and wild-type mice in the tail-flick test and von Frey hair test. There was no significantly difference in the relative change in pain sensitivity between wild-type and D3 receptor mutant mice in both the tail-flick test and von Frey hair test following amphetamine administration. These results suggest that the D3 receptor regulates the transmission of nociception. Moreover, amphetamine can lower pain threshold in mice.

S1738 Role of D2 Dopamine Receptors in the Pathogenesis of Experimental Ulcerative Colitis: Implication of Colonic Vascular Permeability

S1738 Role of D2 Dopamine Receptors in the Pathogenesis of Experimental Ulcerative Colitis: Implication of Colonic Vascular Permeability

Role of Dopamine D1Receptors and Extracellular Signal Regulated Kinase in the Motivational Properties of Acetaldehyde as Assessed by Place Preference Conditioning

The role of dopamine D1 receptors and Extracellular signal Regulated Kinase (ERK) in the motivational properties of drugs can be studied by place-conditioning. Recent advances have shown that the motivational properties of ethanol, determined by place-conditioning, are mediated by its metabolic conversion into acetaldehyde. To date, the role of D1 receptors and ERK activation in acetaldehyde-elicited place preference has not been determined. The aim of this study was to assess the role of D1 receptors blockade and MEK inhibition in the acquisition of acetaldehyde-elicited conditioned place preference. Male Sprague-Dawley rats were subjected to repeated pairings with 1 compartment of the conditioning apparatus immediately following acetaldehyde (20 mg/kg i.g.) or ethanol (1 g/kg i.g.) administration. The D1 receptor antagonist, SCH 39166 (50 microg/kg s.c.), was administered 10 minutes before acetaldehyde or ethanol administration. In order to study the role of activated ERK in the acetaldehyde-elicited place preference, rats were administered the MEK inhibitor, PD98059 (1, 30, and 90 microg i.c.v.), 10 or 30 minutes before acetaldehyde. To verify the specificity of these effects, we also studied whether PD98059 pretreatment could affect morphine (1 mg/kg s.c.)-elicited place preference. Both acetaldehyde and ethanol elicited significant place preferences and these were prevented by pretreatment with SCH 39166. In addition, pretreatment with PD98059, dose (30 and 90 but not 1 microg i.c.v.) and time (10 but not 30 minutes before) dependently, prevented the acquisition of acetaldehyde- and significantly reduced the acquisition of morphine-elicited conditioned place preference. These results confirm that acetaldehyde and ethanol elicit conditioned place preference and demonstrate that D1 receptors are critically involved in these effects. Furthermore, the finding that PD98059 prevents the acquisition of acetaldehyde-elicited conditioned place preference highlights the importance of the D1 receptor-ERK pathway in its motivational effects.

Functional role of dopamine D1 receptors in information processing through the basal ganglia analyzed by neuronal recording from transgenic mice in awake state

Functional role of dopamine D1 receptors in information processing through the basal ganglia analyzed by neuronal recording from transgenic mice in awake state

Role of dopamine D1 receptors in caffeine‐mediated ERK phosphorylation in the rat brain

The aim of this research was to study the role of dopamine D(1) receptors in caffeine elicited ERK phosphorylation in the prefrontal and other cortical (cingulate and motor) and subcortical (shell and core of the nucleus accumbens) regions. To this end, caffeine (3 and 10 mg/kg) was administered before phosphoERK immunohistochemistry. Caffeine dose-dependently increased the number of phosphoERK-positive neurons in the prefrontal and cingulate cortices but not in the secondary motor cortex and in the nucleus accumbens shell and core. The dopamine D(1) receptor antagonist, SCH 39166 (50 microg/kg), fully prevented phosphoERK activation by caffeine (10 mg/kg) in the superficial and deep layers of the prefrontal cortex but failed to prevent it in the cingulate cortex. Given that phosphoERK can be regarded as a postsynaptic marker of neuronal activation, the present results indicate that psychotropic properties of caffeine may result from the activation of prefrontal, via dopamine D(1) receptors, and cingulate cortices. Failure of caffeine to activate ERK in the nucleus accumbens further supports, indirectly, the observation that caffeine fails to activate dopamine transmission in this structure and is consistent with the tenet that caffeine lacks of true addictive properties.

Search for novel antipsychotic drugs: dopamine forever?

During the history of antipsychotic medications, the dopamine D2 receptor has been the crucial main target of drug action. Typical antipsychotics, which dominated the first 25 years of antipsychotic treatment as well as atypical antipsychotics, medications of the last three decades, all retained dopamine D2 receptor antagonism as the basic mode of action. Whether the superior side-effect profile (fewer extrapyramidal symptoms) of atypical antipsychotic agents is due to their serotonin 5-HT2A receptor antagonist activity or to their looser binding to the dopamine D2 receptor is still a matter of debate. Brain imaging studies demonstrating a strong relationship between dopamine D2 receptor occupancy and clinical effects and side effects of antipsychotics gave fundamental support for a central role of dopamine D2 receptors in the pathology and therapy of schizophrenia. The clinical failure of alternative approaches lacking the D2 component, such as selective serotonin 5-HT2A and dopamine D4 receptor antagonists further pointed at the indispensable role of D2 antagonism. The recently developed atypical antipsychotic agent, aripiprazole, while preserving the predominant D2 action, introduced a new pharmacological approach: dopamine D2 receptor partial agonism. An appropriate degree of partial agonism presumably results in effective blockade of overstimulated dopamine D2 receptors and improvement in psychotic symptoms, while it prevents the induction of extrapyramidal side effects or secondary negative symptoms by avoiding complete silencing of dopaminergic transmission. In recent years, the glutamatergic hypothesis for the pathology of the disease has gradually gained acceptance. Beside theoretical considerations, this concept was initially fuelled by some successful trials with the glutamate NMDA receptor co-agonists glycine, D-cycloserine and D-serine on the negative symptoms of the disease. However, their efficacy was modest and these compounds were still applied as adjunct therapy to the standard D2 dopaminergic antipsychotics. The most recent and, perhaps, most promising ''challenge'' to the D2 centred therapy of schizophrenia has been the successful proof of concept trial with the selective metabotropic glutamatergic receptor mGlu2/mGlu3 agonist prodrug compound, LY2140023. However, confirmation of the clinical efficacy of the compound is still awaited, and it has been raised that the compound may eventually affect - though indirectly - dopaminergic mechanisms. It seems, despite several burial attempts and attractive alternative hypotheses and tremendous drug development efforts, the therapy of schizophrenia cannot - so far - detach itself from the dopaminergic system.

Penile erection and yawning induced by dopamine D2-like receptor agonists in rats: influence of strain and contribution of dopamine D2, but not D3 and D4 receptors

Dopamine (DA) is implicated in penile erection (PE) and yawning (YA) in rats through activation of D2-like receptors. However, the exact role of each subtype (D2, D3 and D4) of this receptor family in PE/YA is still not clearly elucidated. We recorded concomitantly PE and YA after treatment with agonists with various levels of selectivity for the different subtypes of D2-like receptors. In addition, we investigated the efficacy of antagonists with selective or preferential affinity for each of the three receptor subtypes to prevent apomorphine-induced PE and YA. Wistar rats were more sensitive than Long-Evans rats to the erectogenic activity of the nonselective DA agonist apomorphine (0.01-0.08 mg/kg), whereas Sprague-Dawley rats were insensitive. However, all the three strains were equally sensitive to apomorphine-induced YA. In Wistar rats, apomorphine (0.01-0.63 mg/kg), the D2/D3 agonists quinelorane and (+)7-OH-DPAT (0.000625-10 mg/kg) or PD 128,907 (0.01-10 mg/kg), but not the D4 agonists PD-168,077, RO-10-5824 and ABT-724 (0.04-0.63 mg/kg), produced PE and YA with bell-shaped dose-response curves. Similarly, ABT-724 and CP226-269 (another D4 agonist) failed to elicit PE and YA in Sprague-Dawley rats. Furthermore, in Wistar rats, PE and YA elicited by apomorphine (0.08 mg/kg) were not modified by selective D3 (S33084 and SB-277011, 0.63-10 mg/kg) or D4 (L-745,870 and RBI-257, 0.63-2.5 mg/kg) antagonists, but were prevented by the preferential D2 blocker L-741,626 (near-full antagonism at 2.5 mg/kg). The present data do not support a major implication of either DA D3 or D4 receptors in the control of PE and YA in rats, but indicate a preponderant role of DA D2 receptors.

PRECLINICAL STUDY: Long‐term haloperidol treatment (but not risperidone) enhances addiction‐related behaviors in mice: role of dopamine D2 receptors

The high prevalence of psychostimulant abuse observed in schizophrenic patients may be related to the development of mesolimbic dopaminergic supersensitivity (MDS) or nigrostriatal dopaminergic supersensitivity (NDS) in response to the chronic blockade of dopamine receptors produced by typical neuroleptic treatment. We compared the effects of withdrawal from long-term administration of the typical neuroleptic haloperidol (Hal) and/or the atypical agent risperidone (Ris) on MDS and NDS, behaviorally evaluated by amphetamine-induced locomotor stimulation (AILS) and apomorphine-induced stereotypy (AIS) in mice, respectively. We further evaluated the duration of MDS and investigated the specific role of dopamine D2 receptors in this phenomenon by administering the D2 agonist quinpirole (Quin) to mice withdrawn from long-term treatment with these neuroleptics. Withdrawal (48 hours) from long-term (20 days) Hal (0.5 mg/kg i.p.) (but not 0.5 mg/kg Ris i.p.) treatment potentiated both AILS and AIS. Ris co-administration abolished the potentiation of AILS and AIS observed in Hal-withdrawn mice. Ten days after withdrawal from long-term treatment with Hal (but not with Ris or Ris + Hal), a potentiation in AILS was still observed. Only Hal-withdrawn mice presented an attenuation of locomotor inhibition produced by Quin. Our data suggest that the atypical neuroleptic Ris has a pharmacological property that counteracts the compensatory MDS and NDS developed in response to the chronic blockade of dopamine receptors imposed by Ris itself or by typical neuroleptics such as Hal. They also indicate that MDS may be long lasting and suggest that an upregulation of dopamine D2 receptors in response to long-term treatment with the typical neuroleptic is involved in this phenomenon.

A role for dopamine D2 receptors in reversal learning

Reversal learning has been shown to require intact serotonergic innervation of the forebrain neocortex. Whether dopamine acting through D2 receptors plays a complementary role in this anatomic area is still unclear. Here we show that mice lacking dopamine D2 receptors exhibited significantly impaired performance in the reversal learning phase of an attention-set-shifting task (ASST) and that wild type mice treated chronically with the D2-like receptor antagonist haloperidol exhibited the same cognitive deficit. The test-phase-specific deficits of D2 mutants and haloperidol-treated mice were also accompanied by deficits in the induction of expression of early growth response gene 2 (egr-2), a regulatory transcription factor previously shown to be selectively induced in the ventrolateral orbital frontal cortex and the pre- and infralimbic medial prefrontal cortex of ASST-tested mice. D2-receptor knockout mice and haloperidol-treated wild type, however, exhibited lower egr-2 expression in these anatomic regions after completion of an ASST-test phase that required reversal learning but not after completion of set-shifting phases without rule reversals. In contrast, mice treated chronically with clozapine, an atypical neuroleptic drug with lower D2-receptor affinity and broader pharmacological effects, had deficits in compound discrimination phases of the ASST, but also these deficits were accompanied by lower egr-2 expression in the same anatomic subregions. Thus, the findings indicate that egr-2 expression is a sensitive indicator of test-phase-specific performance in the ASST and that normal function of D2 receptors in subregions of the orbital frontal and the medial prefrontal cortex is required for cognitive flexibility in tests involving rule reversals.

Delay of Ejaculation Induced by SB-277011, a Selective Dopamine D3 Receptor Antagonist, in the Rat

Dopamine (DA) plays a key role in different aspects of the male sexual response, including sexual motivation and arousal, penile erection, and ejaculation. The modalities of action of DA are however unclear, although the various DA receptors may differentially mediate the activity of DA in different aspects of the male sexual response. To clarify the role of DA D(3) receptors in the control of the male sexual response. The effects of a highly selective DA D(3) receptors antagonist (SB-277011; intraperitoneal) were tested in experimental paradigms exploring several aspects of the male sexual response in (i) anesthetized rats using 7-hydroxy-N,N-di-n-propylaminotetralin to induce ejaculation and (ii) conscious rats using sexual incentive motivation and mating tests. Physiological markers of erection and emission and expulsion phases of ejaculation were measured in anesthetized rats. Behavioral parameters of sexual incentive motivation and mating tests were quantified. In anesthetized rats, we found that SB-277011 specifically and dose-dependently inhibited the expulsion phase of ejaculation without impairing either emission phase or erection, and this resulted in delayed ejaculation. Administration of SB-277011 had no effect on the spontaneous preference that males displayed for sexually receptive females as shown in sexual incentive motivation test. Delayed ejaculation was confirmed when male rats were administered with the highest dose of SB-277011 (10 mg/kg) in mating test, where males were free to copulate with estrous females. In addition, the refractory period following ejaculation was lengthened in rats treated with SB-277011. As a whole, the present data demonstrate the specific and primary role of D(3) receptors in the expulsion phase of ejaculation and provide preclinical evidence for the investigation of the therapeutic potential of D(3) antagonism for treating premature ejaculation.

Specific role of dopamine D1 receptors in spinal network activation and rhythmic movement induction in vertebrates

Dopamine (DA) is well-recognized for its determinant role in the modulation of various brain functions. DA was also found in in vitro isolated invertebrate preparations to activate per se the central pattern generator for locomotion. However, it is less clear whether such a role as an activator of central neural circuitries exists in vertebrate species. Here, we studied in vivo the effects induced by selective DA receptor agonists and antagonists on hindlimb movement generation in mice completely spinal cord-transected (Tx) at the low-thoracic level (Th9/10). Administration of D1/D5 receptor agonists (0.5-2.5 mg kg(-1), i.p.) was found to acutely elicit rhythmic locomotor-like movements (LMs) and non-locomotor movements (NLMs) in untrained and non-sensory stimulated animals. Comparable effects were found in mice lacking the D5 receptor (D5KO) whereas D1/D5 receptor antagonist-pretreated animals (wild-type or D5KO) failed to display D1/D5 agonist-induced LMs. In contrast, administration of broad spectrum or selective D2, D3 or D4 agonists consistently failed to elicit significant hindlimb movements. Overall, the results clearly show in mice the existence of a role for D1 receptors in spinal network activation and corresponding rhythmic movement generation.

Role of dopamine D1 receptors in the prefrontal dorsal agranular insular cortex in mediating cocaine self-administration in rats

Orbital/insular areas of the prefrontal cortex (PFC) are implicated in cocaine addiction. However, the role of dopamine D1 receptors in mediating cocaine self-administration in these sub-regions remains unknown. To define the role of the dorsal agranular insular (AId) sub-region of the PFC, we investigated the effects of D1 receptor manipulation on self-administration behavior maintained by cocaine and cocaine-related stimuli. Rats were trained to lever press for cocaine (1 mg/kg) under a fixed-interval 5-min (fixed-ratio 5:S) second-order schedule of reinforcement in the presence of conditioned light cues and contextual sound cues. Intra-AId infusions of vehicle, the D1-like receptor agonist SKF 81297 (0.1, 0.2, 0.4 microg/side) or the D1-like receptor antagonist SCH 23390 (1.0, 2.0, 4.0 microg/side), were administered prior to 1-h self-administration test sessions. Food-maintained responding under a second-order schedule was examined in separate rats to determine if pretreatment with D1 ligands produced general impairments in responding. Infusion of SKF 81297 (0.2 and 0.4 microg/side) reduced active lever responses during the first 30 min of 1-h test sessions, but did not influence cocaine intake. Infusion of 4.0 microg/side SCH 23390 reduced active lever responses and cocaine intake throughout the 1-h test sessions. Additionally, this dose of SCH 23390 disrupted food-maintained responding and intake. D1 receptor agonists and antagonists in the AId have diverse consequences and time courses of action. D1 receptor stimulation in the AId may reduce the motivating influence of cocaine-related stimuli on responding whereas D1 receptor blockade in this PFC sub-region produces global disruptions in behavior.

Cannabis, cocaine, and visuomotor integration: Evidence for a role of dopamine D1 receptors in binding perception and action

The primate cortex represents and produces events in a distributed way, which calls for a mechanism that integrates their features into coherent structures. Visuomotor integration seems to be driven by dopaminergic (DA) pathways but which subsystems are involved is currently unknown. The present study compared the impact of the recreational use of two drugs on visuomotor integration: cannabis, which primarily targets dopaminergic D1 receptors, and cocaine, which mainly targets D2 receptors. Our findings show that cannabis but not cocaine use affects the strength of the binding between task-relevant stimulus features and the accompanying response. In contrast, cocaine but not cannabis use eliminates the inhibition of return. The observed pattern suggests that visuomotor integration is driven by DA/D1, but not DA/D2 receptor systems.

P.4.b.007 Spontaneous alternation behaviour as an animal model of OCD; the role of dopamine D2 receptors in nucleus accumbens

Many factors contribute to sleep disturbance among young adults. Social media (SM) use is increasing rapidly, and little is known regarding its association with sleep disturbance.In 2014 we assessed a nationally representative sample of 1788 U.S. young adults ages 19–32. SM volume and frequency were assessed by self-reported minutes per day spent on SM (volume) and visits per week (frequency) using items adapted from the Pew Internet Research Questionnaire. We assessed sleep disturbance using the brief Patient-Reported Outcomes Measurement Information System (PROMIS®) sleep disturbance measure. Analyses performed in Pittsburgh utilized chi-square tests and ordered logistic regression using sample weights in order to estimate effects for the total U.S. population.In models that adjusted for all sociodemographic covariates, participants with higher SM use volume and frequency had significantly greater odds of having sleep disturbance. For example, compared with those in the lowest quartile of SM use per day, those in the highest quartile had an AOR of 1.95 (95% CI = 1.37–2.79) for sleep disturbance. Similarly, compared with those in the lowest quartile of SM use frequency per week, those in the highest quartile had an AOR of 2.92 (95% CI = 1.97–4.32) for sleep disturbance. All associations demonstrated a significant linear trend.The strong association between SM use and sleep disturbance has important clinical implications for the health and well-being of young adults. Future work should aim to assess directionality and to better understand the influence of contextual factors associated with SM use.

Accumbal dopamine D2 receptors are important for sensorimotor gating in C3H mice

One operational measure of sensorimotor gating that is deficient in many psychiatric disorders is prepulse inhibition (PPI) of the startle response. To investigate the role of dopamine D1 and D2 receptors within the nucleus accumbens (NAC) in sensorimotor gating in mice, we infused dopamine D1 and D2 receptor agonists (dihydrexidine and quinpirole respectively) directly into the NAC and measured the effects on PPI and on prepulse facilitation. Quinpirole infusions increased PPI and attenuated prepulse facilitation, whereas dihydrexidine had no effects. These results stand in contrast to data after systemic injections in mice and rats and intra-accumbal infusions in rats, suggesting that the role of dopamine D2 receptors within the NAC in mice differs from their role in rats.

Role of dopamine D1 receptors in novelty seeking in adult female Long-Evans rats

Adult Long-Evans ovariectomized female rats received injections of the DA D1 antagonist SCH 23390 (0, 0.03 and 0.3 mg/kg, i.p.) and were observed in an open field apparatus (OFA) with a novel object. Results indicate that a significant effect of SCH 23390 was found on several measures of novelty seeking and activity, with the high dose producing a significant decrease in (1) approaches to and (2) rears while approaching the novel object, (3) latency to interact with the novel object, (4) in time interacting with the novel object, (5) anxious behavior (as measured by rears) and (6) locomotor activity (LMA), as compared to both the saline and low dose. Interestingly, the effects of SCH 23390 on approaches and rears were not significant when LMA was factored into the analysis (repeated measures ANCOVA), however, marked results were still found on time interacting with the novel object. These data demonstrate that SCH 23390 produced dose-dependent effects on novelty seeking that were independent of LMA, implicating D1 receptors in the incentive-motivational aspect of novelty seeking in adult gonadectomized female rats.