Roles of nucleus accumbens shell and core in footshock-induced stress altering behavioral sensitization by methamphetamine in acquisition and testing: Running head: stress, nucleus accumbens, and behavioral sensitization.

How the subregions of the nucleus accumbens (NAc) shell and core and stress are involved in behavioral sensitization induced by psychostimulants remains unclear. The present study manipulated methamphetamine (MAMPH) injections, lesions of the NAc shell or core, and footshock-treatment-induced stress to address this issue. The present data showed that during the acquisition phase, MAMPH injections, lesions of the NAc shell, and footshock treatments induced hyperactivity for the NAc shell. For the NAc core, MAMPH injections induced hyperactivity; however, lesions of the NAc core did not affect locomotor activity. Footshock treatments disrupted hyperactivity of behavioral sensitization. During the testing phase, MAMPH injections, lesions of the NAc shell, and footshock-treatment-induced stress facilitated hyperactivity for the NAc shell. For the NAc core, MAMPH injections and footshock-treatment-induced stress increased hyperactivity. However, the lesion of the NAc core did not affect locomotor activity. In conclusion, MAMPH injections and footshock-treatment-induced stress play an excitatory role for the NAc shell in acquisition and testing. For the NAc core, footshock-treatment-induced stress plays an inhibitory role in acquisition but an excitatory role in testing. The NAc core was not involved in MAMPH-induced behavioral sensitization in acquisition and testing. The NAc shell plays an inhibitory role in acquisition and testing phases. The present data might provide some insights for drug addiction. The results should be discussed further.

Selective Lesioning of Nuclear Factor-κB Activated Cells in the Nucleus Accumbens Shell Attenuates Alcohol Place Preference.

Nuclear factor κ-light chain enhancer of activated B cells (NF-κB) is a transcription factor commonly associated with innate immunity and is activated by infection and inflammation. NF-κB has recently gained attention as a mediator of complex psychiatric phenomena such as stress and addiction. In regards to alcohol, most research on NF-κB has focused on neurotoxicity and few studies have explored the role of NF-κB in alcohol reward, reinforcement, or consumption. In these studies, we used conditioned place preference to assess the activity of NF-κB in response to rewarding doses of alcohol. To measure NF-κB activity we used a line of transgenic mice that express the LacZ gene under the control of an NF-κB-regulated promoter. In these animals, staining for ß-galactosidase (ß-gal) identifies cells in which NF-κB has been activated. We then used the Daun02 inactivation method to specifically silence NF-κB-expressing cells during place preference conditioning. Daun02 is an inactive prodrug that is converted to the inhibitory molecule daunorubicin by ß-gal. After alcohol place conditioning, we observed increased ß-gal staining in the nucleus accumbens (NAC) shell and dorsal raphe nucleus, and found that disruption of NF-κB-expressing cells using Daun02 attenuated the development of alcohol place preference when infused into the NAC shell following conditioning sessions. We found this effect to be regionally and temporally specific. These results suggest that, in addition to its role in alcohol-induced neurotoxicity, NF-κB mediates the development of alcohol place preference via its actions in the NAC shell.

Nucleus accumbens core lesions induce sub-optimal choice and reduce sensitivity to magnitude and delay in impulsive choice tasks.

The nucleus accumbens core (NAc) has long been recognized as an important contributor to the computation of reward value that is critical for impulsive choice behavior. Impulsive choice refers to choosing a smaller-sooner (SS) over a larger-later (LL) reward when the LL is more optimal in terms of the rate of reward delivery. Two experiments examined the role of the NAc in impulsive choice and its component processes of delay and magnitude processing. Experiment 1 delivered an impulsive choice task with manipulations of LL reward magnitude, followed by a reward magnitude discrimination task. Experiment 2 tested impulsive choice under manipulations of LL delay, followed by temporal bisection and progressive interval tasks. NAc lesions, in comparison to sham control lesions, produced suboptimal preferences that resulted in lower reward earning rates, and led to reduced sensitivity to magnitude and delay within the impulsive choice task. The secondary tasks revealed intact reward magnitude and delay discrimination abilities, but the lesion rats persisted in responding more as the progressive interval increased during the session. The results suggest that the NAc is most critical for demonstrating good sensitivity to magnitude and delay, and adjusting behavior accordingly. Ultimately, the NAc lesions induced suboptimal choice behavior rather than simply promoting impulsive choice, suggesting that an intact NAc is necessary for optimal decision making.

Effect of accumbens nucleus shell lesioning on bitemporal lobe epilepsy in rat model.

INTRODUCTION: To explore the effect of accumbens nucleus shell (ACbSh) lesioning on bitemporal lobe epilepsy. MATERIAL AND METHODS: Adult Wistar rats (male) were enrolled and randomly assigned into the control group and epilepsy groups with multiple time-points. Lithium-pilocarpine was used to establish the rat epilepsy model, while the control group received an equal amount of saline. Ibotenic acid stereotaxic injection was performed to cause accumbens nucleus shell lesioning for specific groups. Cascade software was used for electroencephalogram (EEG) examination. Fluoro-Jade C staining was performed to examine neuronal degeneration. RESULTS: Latency period of the epilepsy in epilepsy groups was 15.3 ± 1.1 min, and epilepsy intensity was 4.8 ± 0.5 events/ 12 h. ACbSh lesioning significantly reduced aggressive behavior. Compared with epilepsy groups without ACbSh lesioning, ACbSh lesioning significantly decreased epileptic seizures and reduced epileptic duration (p < 0.05). EEG showed that there were still sharp waves in the hippocampus and amygdala region after ACbSh lesioning, but epileptic discharge in prefrontal cortex was significantly decreased (p < 0.05), while epilepsy groups without ACbSh lesioning had more sharp waves in the prefrontal cortex, hippocampus and amygdala region. Fluoro-Jade C staining showed that ACbSh lesioning significantly decreased grades of neuronal degeneration (p < 0.05). CONCLUSIONS: Recurrent epilepsy caused neuronal degeneration via ACbSh region-related pathways, and ACbSh lesioning could mitigate epilepsy-caused neuronal degeneration by reducing epileptic discharge.

Central GLP-1 receptor activation modulates cocaine-evoked phasic dopamine signaling in the nucleus accumbens core.

Drugs of abuse increase the frequency and magnitude of brief (1-3s), high concentration (phasic) dopamine release events in terminal regions. These are thought to be a critical part of drug reinforcement and ultimately the development of addiction. Recently, metabolic regulatory peptides, including the satiety signal glucagon-like peptide-1 (GLP-1), have been shown to modulate cocaine reward-driven behavior and sustained dopamine levels after cocaine administration. Here, we use fast-scan cyclic voltammetry (FSCV) to explore GLP-1 receptor (GLP-1R) modulation of dynamic dopamine release in the nucleus accumbens (NAc) during cocaine administration. We analyzed dopamine release events in both the NAc shell and core, as these two subregions are differentially affected by cocaine and uniquely contribute to motivated behavior. We found that central delivery of the GLP-1R agonist Exendin-4 suppressed the induction of phasic dopamine release events by intravenous cocaine. This effect was selective for dopamine signaling in the NAc core. Suppression of phasic signaling in the core by Exendin-4 could not be attributed to interference with cocaine binding to one of its major substrates, the dopamine transporter, as cocaine-induced increases in reuptake were unaffected. The results suggest that GLP-1R activation, instead, exerts its suppressive effects by altering dopamine release - possibly by suppressing the excitability of dopamine neurons. Given the role of NAc core dopamine in the generation of conditioned responses based on associative learning, suppression of cocaine-induced dopamine signaling in this subregion by GLP-1R agonism may decrease the reinforcing properties of cocaine. Thus, GLP-1Rs remain viable targets for the treatment and prevention of cocaine seeking, taking and relapse.

Evaluation of White Matter Injury Patterns Underlying Neuropsychiatric Symptoms after Mild Traumatic Brain Injury.

PURPOSE: To determine if a central axonal injury underlies neuropsychiatric symptoms after mild traumatic brain injury (mTBI) by using tract-based spatial statistics analysis of diffusion-tensor images. MATERIALS AND METHODS: The institutional review board approved this study, with waiver of informed consent. Diffusion-tensor imaging and serial neurocognitive testing with the Immediate Post-Concussion Assessment and Cognitive Testing evaluation were performed in 45 patients with mTBI (38 with irritability, 32 with depression, and 18 with anxiety). Control subjects consisted of 29 patients with mTBI without neuropsychiatric symptoms. Fractional anisotropy and diffusivity maps were analyzed by using tract-based spatial statistics with a multivariate general linear model. Diffusion-tensor imaging findings were correlated with symptom severity, neurocognitive test scores, and time to recovery with the Pearson correlation coefficient. RESULTS: Compared with control subjects, patients with mTBI and depression had decreased fractional anisotropy in the superior longitudinal fasciculus (P = .006), white matter around the nucleus accumbens (P = .03), and anterior limb of the internal capsule (P = .02). Patients with anxiety had diminished fractional anisotropy in the vermis (P = .04). No regions of significantly decreased fractional anisotropy were seen in patients with irritability relative to control subjects. Injury in the region of the nucleus accumbens inversely correlated with recovery time in patients with depression (r = -0.480, P = .005). CONCLUSION: Unique white matter injury patterns were seen for two major posttraumatic neuropsychiatric symptoms. Injury to the cerebellar vermis in patients with mTBI and anxiety may indicate underlying dysfunction in primitive fear conditioning circuits in the cerebellum. Involvement of the nucleus accumbens in depression after mTBI may suggest an underlying dysfunctional reward circuit that affects the prognosis in these patients.

6-Hydroxydopamine lesions of the anteromedial ventral striatum impair opposite-sex urinary odor preference in female mice.

Rodents rely upon their olfactory modality to perceive opposite-sex pheromonal odors needed to motivate courtship behaviors. Volatile and nonvolatile components of pheromonal odors are processed by the main (MOS) and accessory olfactory system (AOS), respectively, with inputs converging in the medial amygdala (Me). The Me in turn targets the mesolimbic dopamine system, including the nucleus accumbens core (AcbC) and shell (AcbSh), the ventral pallidum (VP), medial olfactory tubercle (mOT) and ventral tegmental area (VTA). We hypothesized that pheromone-induced dopamine (DA) release in the ventral striatum (particularly in the mAcb and mOT) may mediate the normal preference of female mice to investigate male pheromones. We made bilateral 6-OHDA lesions of DA fibers innervating either the mAcb alone or the mAcb+mOT in female mice and tested estrous females' preference for opposite-sex urinary odors. We found that 6-OHDA lesions of either the mAcb alone or the mAcb+mOT significantly reduced the preference of sexually naïve female mice to investigate breeding male urinary odors (volatiles as well as volatiles+nonvolatiles) vs. estrous female urinary odors. These same neurotoxic lesions had no effect on subjects' ability to discriminate between these two urinary odors, on their locomotor activity, or on their preference for consuming sucrose. The integrity of the dopaminergic innervation of the mAcb and mOT is required for female mice to prefer investigating male pheromones.

Performance of compulsive behavior in rats is not a unitary phenomenon - validation of separate functional components in compulsive checking behavior.

A previous analysis of the quinpirole sensitisation rat model of obsessive-compulsive disorder revealed that the behavioral phenotype of compulsive checking consists of three constitutive components - vigor of checking performance, focus on the task of checking, and satiety following a bout of checking. As confirmation of this analysis, the aim of the present study was to reconstitute, without quinpirole treatment, each of the putative components, with the expectation that these would self-assemble into compulsive checking. To reconstitute vigor and satiety, the employed treatment was a bilateral lesion of the nucleus accumbens core (NAc), as this treatment was shown previously to exaggerate these components. To reconstitute focus, the employed treatment was a low dose of the serotonin-1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin hydrochloride (DPAT) (0.0625 mg/kg), as high doses of this drug induce compulsive behavior and exacerbate focus. Results showed that injection of DPAT to NAc lesion rats did yield compulsive checking. Neither the drug alone nor the NAc lesion by itself produced compulsive checking. The demonstrated synthesis of compulsive checking by the combined treatment of low-dose DPAT and NAc lesion strengthened the previous fractionation of the model obsessive-compulsive disorder phenotype into three constitutive components, and suggested a role for serotonin-1A receptors outside the NAc in enhanced focus on the task of checking.

Lesions of the nucleus accumbens disrupt reinforcement omission effects in rats.

The reinforcement omission effects (ROEs) have been attributed to both motivational and attentional consequences of the surprising reinforcement omission. Some studies have been showed amygdala is part of a circuit involved in the ROEs modulation. The view that amygdala lesions interfere with the ROEs is supported by evidence involving amygdala in responses correlated with motivational processes. These processes depend on the operation of separate amygdala areas and their connections with other brain systems. It has been suggested the interaction between the amygdala and the nucleus accumbens (NAC) is important to the modulation of motivational processes. Recent neuroimaging studies in human revealed reward delivery enhances activity of subcortical structures (NAC and amygdala), whereas reward omission reduces the activity in these same structures. The present study aimed to clarify whether the mechanisms related to ROEs depend on NAC. Prior to acquisition training, rats received bilateral excitotoxic lesions of NAC (NAC group) or sham lesions (Sham group). Following postoperative recovery, the rats were trained on a fixed-interval with limited hold signaled schedule of reinforcement. After acquisition of stable performance, the training was changed from 100% to 50% schedule of reinforcement. Both NAC and Sham groups presented the ROEs. However, after nonreinforcement, the response rates of the NAC group were lower than those registered in the Sham group. The performance of the NAC group decreased in the period following nonreinforcement when compared to the period preceding reinforcement omission. These findings suggest the NAC is part of the neural substrate involved in the ROEs modulation.

Opposing effects of 5,7-DHT lesions to the core and shell of the nucleus accumbens on the processing of irrelevant stimuli.

There is good evidence that forebrain serotonergic systems modulate cognitive flexibility. Latent inhibition (LI) is a cross-species phenomenon which manifests as poor conditioning to a stimulus that has previously been experienced without consequence and is widely considered an index of the ability to ignore irrelevant stimuli. While much research has focused on dopaminergic mechanisms underlying LI, there is also considerable evidence of serotonergic modulation. However, the neuroanatomical locus of these effects remains poorly understood. Previous work has identified the nucleus accumbens (NAc) as a key component of the neural circuit underpinning LI and furthermore, this work has shown that the core and shell subregions of the NAc contribute differentially to the expression of LI. To examine the role of the serotonergic input to NAc in LI, we tested animals with 5,7-dihydroxytryptamine (5,7-DHT) lesions to the core and shell subregions on LI assessed under experimental conditions that produce LI in shams and subsequently with weak stimulus pre-exposure designed to prevent the emergence of LI in shams. We found that serotonergic deafferentation of the core disrupted LI whereas 5,7-DHT lesions to the shell produced the opposite effect and potentiated LI.

Motivational states influence effort-based decision making in rats: the role of dopamine in the nucleus accumbens.

Decision-making policies are subject to modulation by changing motivational states. However, so far, little is known about the neurochemical mechanisms that bridge motivational states with decision making. Here we examined whether dopamine (DA) in the nucleus accumbens core (AcbC) modulates the effects of motivational states on effort-based decision making. Using a cost-benefit T-maze task in rats, we examined the effects of AcbC DA depletions on effort-based decision making, in particular on the sensitivity of effort-based decision making to a shift from a hungry to a sated state. The results demonstrated that, relative to sham controls, rats with AcbC DA depletion in a hungry as well as in a sated state had a reduced preference for effortful but large-reward action. This finding provides further support for the notion that AcbC DA regulates how much effort to invest for rewards. Importantly, our results further revealed that effort-based decision making in lesioned rats, as in sham controls, was still sensitive to a shift from a hungry to a sated state; that is, their preferences for effortful large-reward actions became lower after a shift from a restricted to a free-feeding regimen. These finding indicate that AcbC DA is not necessarily involved in mediating the effects of a shift in motivational state on decision-making policies.

The role of the nucleus accumbens in knowing when to respond.

While knowing what to expect is important, it is equally important to know when to expect it and to respond accordingly. This is apparent even in simple Pavlovian training situations in which animals learn to respond more strongly closer to reward delivery. Here we report that the nucleus accumbens core, an area well-positioned to represent information about the timing of impending rewards, plays a critical role in this timing function.

Noise benefit in prepulse inhibition of the acoustic startle reflex.

RATIONALE: Under some conditions, external sensory noise enhances cognitive functions, a phenomenon possibly involving stochastic resonance and/or enhanced central dopamine transmission. Prepulse inhibition (PPI) of the startle reflex is a robust measure of sensorimotor gating and can be modulated by activity in the cortex and basal ganglia, including the central dopamine pathways. OBJECTIVES: Previous empirical studies suggest a differential effect of acoustic noise in normal children and children with attention-deficit hyperactivity disorder (ADHD). This study investigated the effect of acoustic noise on PPI and if dopamine transmission interacts with acoustic noise effects in a rat ADHD model. METHODS: The effect of background acoustic noise on acoustic startle response and PPI were measured with a constant prepulse to background noise ratio of 9 dB(A). Spontaneously hypertensive (SH) rats were used as the ADHD model and compared with Wistar and Sprague-Dawley rats. Microdialysis, methylphenidate treatment and 6-OHDA lesions were used to investigate interaction with dopamine transmission. RESULTS: Background noise facilitated PPI differently in SH rats and controls. The prefrontal cortex in SH rats had low basal dopamine concentrations, a high DOPAC/dopamine ratio and blunted dopamine release during PPI testing. Methylphenidate had small, but strain-specific, effects on startle and PPI. Bilateral 6-hydroxydopamine lesions did not alter startle or PPI. CONCLUSIONS: Prefrontal dopamine transmission is altered in SH rats during the sensorimotor gating task of PPI of the acoustic startle, indicating increased dopamine reuptake in this ADHD rat model. We propose that noise benefit could be explored as a non-pharmacological alternative for treating neuropsychiatric disorders.

The role of nucleus accumbens shell in learning about neutral versus excitatory stimuli during Pavlovian fear conditioning.

We studied the role of nucleus accumbens shell (AcbSh) in Pavlovian fear conditioning. Rats were trained to fear conditioned stimulus A (CSA) in Stage I, which was then presented in compound with a neutral stimulus and paired with shock in Stage II. AcbSh lesions had no effect on fear-learning to CSA in Stage I, but selectively prevented learning about the neutral conditioned stimulus (CS) in Stage II. These results add to a growing body of evidence indicating an important role for the ventral striatum in fear-learning. They suggest that the ventral striatum and AcbSh, in particular, directs learning toward or away from a CS as a consequence of how well that CS predicts the shock unconditioned stimulus (US). AcbSh is required to reduce the processing of established predictors, thereby permitting neutral or less predictive stimuli to be learned about.

Nucleus accumbens lesions modulate the effects of methylphenidate.

The psychostimulant methylphenidate (MPD, Ritalin) is the prescribed drug of choice for treatment of ADHD. In recent years, the diagnosis rate of ADHD has increased dramatically, as have the number of MPD prescriptions. Repeated exposure to psychostimulants produces behavioral sensitization in rats, an experimental indicator of a drug's potential liability. In studies on cocaine and amphetamine, this effect has been reported to involve the nucleus accumbens (NAc), one of the nuclei belonging to the motive circuit. The aim of this study was to investigate the role of the NAc on the expression of behavioral sensitization as a response to MPD exposure. In the present study, 20 male Sprague-Dawley rats were divided randomly into three groups: an intact control group, a sham-operated group, and a NAc bilateral electrical lesion group. Locomotor activity was assessed for the first 2h following 2.5mg/kg MPD injection, using open field monitoring systems. Recordings were made during 6 days of continuous MPD administration, and then upon re-challenge with the same dose following 3 days of washout. Acute MPD exposure elicited an increase in locomotor activity in all three groups. However, the NAc lesion group exhibited significantly increased locomotor activity in comparison to sham and control groups. Chronic MPD did not elicit sensitization in the NAc lesion group, while both sham and control groups did exhibit behavioral sensitization to repetitive MPD administration. These findings suggest that the NAc plays a significant role in eliciting locomotor activity as an acute effect of MPD, and in the expression of sensitization due to chronic MPD exposure.

The role of the nucleus accumbens core in impulsive choice, timing, and reward processing.

The present series of experiments aimed to pinpoint the source of nucleus accumbens core (AcbC) effects on delay discounting. Rats were trained with an impulsive choice procedure between an adjusting smaller sooner reward and a fixed larger later reward. The AcbC-lesioned rats produced appropriate choice behavior when the reward magnitude was equal. An increase in reward magnitude resulted in a failure to increase preference for the larger later reward in the AcbC-lesioned rats, whereas a decrease in the larger later reward duration resulted in normal alterations in choice behavior in AcbC-lesioned rats. Subsequent experiments with a peak timing (Experiments 2 and 3) and a behavioral contrast (Experiment 4) indicated that the AcbC-lesioned rats suffered from decreased incentive motivation during changes in reward magnitude (Experiments 2 and 4) and when expected rewards were omitted (Experiments 2 and 3), but displayed intact anticipatory timing of reward delays (Experiments 2 and 3). The results indicate that the nucleus accumbens core is critical for determining the incentive value of rewards, but does not participate in the timing of reward delays.

Selective lesions of the dorsomedial striatum impair serial spatial reversal learning in rats.

Impairments in reversal learning have been attributed to orbitofrontal cortex (OFC) dysfunction in many species. However, the role of subcortical areas interconnected with the OFC such as the striatum remains poorly understood. This study directly evaluated the contribution of core and shell sub-regions of the nucleus accumbens (NAc), dorsomedial (DMS) and dorsolateral (DLS) striatum to reversal learning of an instrumental two-lever spatial discrimination task in rats. Selective NAc core, DMS and DLS lesions were achieved with microinjections of quinolinic acid and NAc shell lesions with ibotenic acid. Damage to NAc core or shell did not affect retention of a previously acquired instrumental spatial discrimination. In contrast, DLS and DMS lesions produced changes in aspects of discrimination performance such as the latency to collect earned food pellets. Neither NAc core or shell lesions nor DLS lesions affected the main indices of reversal performance. Conversely, DMS lesion rats showed a significant impairment in reversal learning. DMS damage increased the number of errors to reach criteria that were perseverative in nature. The deficit in reversal learning in DMS lesion rats was not associated with an impairment to extinguish instrumental responding. There were no effects on spontaneous locomotor activity. Our data are in agreement with recent work showing that lesions of the medial striatum in marmoset monkeys produce perseverative impairments during a serial visual discrimination reversal task and support the hypothesis that dorsomedial striatal dysfunction contributes to pathological perseveration, which is a common feature of many psychiatric disorders.

The role of nucleus accumbens dopamine in outcome encoding in instrumental and Pavlovian conditioning.

Considerable evidence suggests that dopamine in the core subregion of the nucleus accumbens is not only involved in Pavlovian conditioning but also supports instrumental performance. However, it is largely unknown whether NAc dopamine is required for outcome encoding which plays an important role both in Pavlovian stimulus-outcome learning and instrumental action-outcome learning. Therefore, we tested rats with 6-hydroxydopamine (6-OHDA) induced dopamine depletion of the NAc core for their sensitivity to outcome devaluation in a Pavlovian and an instrumental task. Results indicate that 6-OHDA-lesioned animals were sensitive to outcome devaluation in an instrumental task. This finding provides support to the notion that NAc core dopamine may not be crucial in encoding action-outcome associations. However, during instrumental conditioning lever pressing rates in 6-OHDA-lesioned animals were markedly lower which could reflect an impaired behavioral activation. By contrast, after outcome-specific devaluation in a Pavlovian task, performance in 6-OHDA-lesioned animals was impaired, i.e. their magazine-directed responding was non-selectively reduced. One possibility to explain non-selective responding is that NAc core DA depletion impaired the ability of conditioned stimuli to activate the memory of the current value of the reinforcer.

6-hydroxydopamine lesions enhance progesterone-facilitated lordosis of rats and hamsters, independent of effects on motor behavior.

The Ventral Tegmental Area (VTA) is an important brain area for progesterone (P(4))'s effects to facilitate female sexual behavior of rodents. We investigated the importance of dopaminergic neurons in the VTA, and two dopaminergic projection sites, the Nucleus Accumbens (NAc), and Caudate Nucleus of the Striatum (CN), in modulating P(4)-facilitated sex and motor behavior. Ovariectomized (ovx) rats and hamsters, administered estradiol benzoate (10 microg) and P(4) (0, 50, 100, 200, or 500 microg), were tested for motor behavior in a chamber that automatically records horizontal beam breaks, and for sexual behavior in response to a sexually-experienced male. Animals were tested once a week until each P(4) dosage was received; animals then had bilateral 6-hydroxydopamine (6-OHDA) or sham lesions to the VTA, NAc, or CN and were re-tested at each P(4) dosage on subsequent weeks. Fixed brains were stained with cresyl violet and processed for dopamine transporter (DAT) immunoreactivity. The number of cresyl violet stained cells was significantly lower in all 6-OHDA infusion sites compared to non-6-OHDA infusion sites of rats and hamsters. Also, in rats, the number of DAT-immunoreactive neurons was lower in all 6-OHDA infusion sites compared to non-6-OHDA infusion sites. In rats, 6-OHDA but not sham, lesions to the VTA, NAc, or CN produced P(4)-dependent increases in lordosis quotients and resulted in modest increases in motor behavior. In hamsters, 6-OHDA, but not sham, lesions to the VTA, NAc, or CN produced P(4)-dependent increases in total lordosis durations and produced modest decreases in motor behavior. This suggests that the dopaminergic output neurons of midbrain VTA may play an important role in modulation of P(4)-facilitated sexual lordosis among rodents.

Ventral striatum dopamine D2 receptor activity inhibits rat pups' vocalization response to loss of maternal contact.

Most mammalian infants vocalize when isolated. The vocalization promotes caregiver proximity, which is critical to survival. If, before isolation, a rat pup has contact with its dam, its isolation vocalization rate is increased (maternal potentiation) relative to isolation preceded only by littermate contact. Prior work showed that systemic administration of a D2 receptor agonist blocks maternal potentiation at doses that do not alter baseline vocalization. In this study, infusion of quinpirole (2 microg/side) into the nucleus accumbens also blocks maternal potentiation. Infusion of the accumbens with the D2 antagonist raclopride (4 microg/side) prevents systemic quinpirole from blocking potentiation. Quinpirole infusion in the dorsal striatum did not affect maternal potentiation and infusion of raclopride in the dorsal striatum did not reverse the block of maternal potentiation by systemic quinpirole. Vocalization results after a second vehicle infusion on a given day are no different than the results following an initial vehicle infusion, so experimental design can not account for the effects of drug infusions. Because activity level was increased by both dorsal and ventral striatum infusions, activity level can not account for the results.