Stimulation Of Nucleus Accumbens Research Articles

Cross-species brain-wide mapping reveals a conserved and coordinated network engaged by NAc DBS.

Nucleus accumbens (NAc) deep brain stimulation (DBS) has been increasingly explored as a treatment modality for refractory neuropsychiatric disorders. Uncovering the accumbens network that is engaged by DBS is a critical step forward in understanding how modulating this important node impacts the broader mesocorticolimbic circuit. Using whole-brain clearing and unbiased, brain-wide neural activity mapping, we found that NAc DBS increases neural activity in a coordinated mesocorticolimbic network in mice. Simultaneous intracranial electrophysiology recordings from the human NAc and brief stimulation epochs of homologous mesocorticolimbic nodes revealed similar connectivity. Altogether, these results identify specific connectivity conserved across species within the mesocorticolimbic circuit that may underlie mechanisms of NAc DBS.

MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens.

MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA's action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like behaviors in the Shank3-deficient mouse model of autism. These findings demonstrate enhancement of empathy-related behaviors by MDMA and implicate 5-HT signaling in the NAc as a core mechanism mediating MDMA's empathogenic effects.

An examination of the effects of nucleus accumbens core nociceptin on appetitive and consummatory motivation for food

The nucleus accumbens (NAc) is a critical region for regulating the appetitive and consummatory aspects of motivated behavior. Previous work has shown differential effects of NAc µ-, δ-, and κ- receptor stimulation on food intake and for shifting motivation within an effort-based choice (EBC) task. However, the motivational role of the nociceptin opioid peptide (NOP) receptor, a fourth member of the opioid receptor family, is less well understood. These experiments therefore characterized the effect of NAc injections of nociceptin, the endogenous ligand for the NOP receptor, on consummatory and appetitive motivation. Three groups of male Sprague-Dawley rats received nociceptin injections into the NAc core prior to testing in a progressive ratio lever pressing task, an EBC task, or a palatable feeding assay. In the feeding experiment, 10 nmol of nociceptin increased consumption in the first 30 min, but this increase was not sustained through the end of the 2-hr session. Additionally, nociceptin injections did not alter breakpoint in the progressive ratio task. However, in the EBC task, nociceptin significantly decreased breakpoint for sugar pellets without affecting consumption of rat chow. These data suggest that NAc NOP receptor stimulation transiently increases consummatory motivation toward palatable diets and inhibits appetitive motivation when alternate food options are freely available. This pattern of effects contrasts with those obtained following NAc stimulation of other opioid receptors, suggesting that the four opioid receptor classes each serve unique roles in modulating food-directed motivation within the NAc core.

Nucleus accumbens D1/D2 circuits control opioid withdrawal symptoms in mice.

The nucleus accumbens (NAc) is the most promising target for drug use disorder treatment. Deep brain stimulation (DBS) of NAc is effective for drug use disorder treatment. However, the mechanisms by which DBS produces its therapeutic effects remain enigmatic. Here, we define a behavioral cutoff criterion to distinguish depressive-like behaviors and non-depressive-like behaviors in mice after morphine withdrawal. We identified a basolateral amygdala (BLA) to NAc D1 medium spiny neuron (MSN) pathway that controls depressive-like behaviors after morphine withdrawal. Furthermore, the paraventricular nucleus of thalamus (PVT) to NAc D2 MSN pathway controls naloxone-induced acute withdrawal symptoms. Optogenetically induced long-term potentiation with κ-opioid receptor (KOR) antagonism enhanced BLA to NAc D1 MSN signaling and also altered the excitation/inhibition balance of NAc D2 MSN signaling. We also verified that a new 50 Hz DBS protocol reversed morphine withdrawal-evoked abnormal plasticity in NAc. Importantly, this refined DBS treatment effectively alleviated naloxone-induced withdrawal symptoms and depressive-like behaviors and prevented stress-induced reinstatement. Taken together, the results demonstrated that input- and cell type-specific synaptic plasticity underlies morphine withdrawal, which may lead to novel targets for the treatment of opioid use disorder.

Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats.

Glucagon-like peptide1 receptor (GLP-1R) agonists have been found to reduce alcohol drinking in rodents and overweight patients with alcohol use disorder (AUD). However, the probability of low semaglutide doses, an agonist with higher potency and affinity for GLP-1R, to attenuate alcohol-related responses in rodents and the underlying neuronal mechanisms is unknown. In the intermittent access model, we examined the ability of semaglutide to decrease alcohol intake and block relapse-like drinking, as well as imaging the binding of fluorescently marked semaglutide to nucleus accumbens (NAc) in both male and female rats. The suppressive effect of semaglutide on alcohol-induced locomotor stimulation and invivo dopamine release in NAc was tested in male mice. We evaluated effect of semaglutide on the invivo release of dopamine metabolites (DOPAC and HVA) and gene expression of enzymes metabolising dopamine (MAOA and COMT) in male mice. In male and female rats, acute and repeated semaglutide administration reduced alcohol intake and prevented relapse-like drinking. Moreover, fluorescently labelled semaglutide was detected in NAc of alcohol-drinking male and female rats. Further, semaglutide attenuated the ability of alcohol to cause hyperlocomotion and to elevate dopamine in NAc in male mice. As further shown in male mice, semaglutide enhanced DOPAC and HVA in NAc when alcohol was onboard and increased the gene expression of COMT and MAOA. Altogether, this indicates that semaglutide reduces alcohol drinking behaviours, possibly via a reduction in alcohol-induced reward and NAc dependent mechanisms. As semaglutide also decreased body weight of alcohol-drinking rats of both sexes, upcoming clinical studies should test the plausibility that semaglutide reduces alcohol intake and body weight in overweight AUD patients. Swedish Research Council (2019-01676), LUA/ALF (723941) from the Sahlgrenska University Hospital and the Swedish brain foundation.

Stimulation of nucleus accumbens 5-HT6 receptors increases both appetitive and consummatory motivation in an effort-based choice task.

Activity of the serotonin 6(5-HT6) receptor impacts food intake and body weight in animal models and has also shown potential as a target for treatment of anhedonia, a symptom of major depressive disorder. The nucleus accumbens (NAc) is a key region involved in motivational processes and has been implicated in the neural mechanisms underlying anhedonia. Here, we assessed the potential role that 5-HT6 receptors in the NAc play in regulating motivation towards food. Rats received surgical implantation of guide cannulas above the NAc shell. On testing days, they were injected with either the selective 5-HT6 agonist EMD 386088 (at 0.0, 1.0, and 4.0 mg/0.5 mL/side) or the 5-HT6 antagonist SB 252585 (at 0, 1.0, and 4.0 µg/0.5 µL/side) prior to completing a 1-h long effort-based choice task. The task simultaneously examined the impact of NAc 5-HT6 receptor manipulation on appetitive motivation, measured as the breakpoint for earning a preferred sugar pellet in a progressive ratio task, and consummatory motivation, quantified as the grams of freely-available rat chow consumed during the session. Stimulation of NAc 5-HT receptors significantly increased both appetitive and consummatory motivation as assessed in this effort-based choice task. In contrast, 5-HT6 antagonism did not affect break point nor the consumption of the freely-available chow. These data suggest that 5-HT6 receptors are functional within the NAc, that their stimulation increases motivated behavior, and that they may therefore be a viable target for the treatment of anhedonia and disorders that inhibit motivational processes.

The Effects of Transcranial Focused Ultrasound Stimulation of Nucleus Accumbens on Neuronal Gene Expression and Brain Tissue in High Alcohol-Preferring Rats.

We investigated the effect of low-intensity focused ultrasound (LIFU) on gene expression related to alcohol dependence and histological effects on brain tissue. We also aimed at determining the miRNA-mRNA relationship and their pathways in alcohol dependence-induced expression changes after focused ultrasound therapy. We designed a case-control study for 100days of observation to investigate differences in gene expression in the short-term stimulation group (STS) and long-term stimulation group (LTS) compared with the control sham group (SG). The study was performed in our Experimental Research Laboratory. 24 male high alcohol-preferring rats 63 to 79days old, weighing 270 to 300g, were included in the experiment. LTS received 50-day LIFU and STS received 10-day LIFU and 40-day sham stimulation, while the SG received 50-day sham stimulation. In miRNA expression analysis, it was found that LIFU caused gene expression differences in NAc. Significant differences were found between the groups for gene expression. Compared to the SG, the expression of 454 genes in the NAc region was changed in the STS while the expression of 382 genes was changed in the LTS. In the LTS, the expression of 32 genes was changed in total compared to STS. Our data suggest that LIFU targeted on NAc may assist in the treatment of alcohol dependence, especially in the long term possibly through altering gene expression. Our immunohistochemical studies verified that LIFU does not cause any tissue damage. These findings may lead to new studies in investigating the efficacy of LIFU for the treatment of alcohol dependence and also for other psychiatric disorders.

The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus

The nucleus accumbens (NAc) is a crucial region in the reward circuit and is related to anhedonia, the pivotal symptom of major depression disorder (MDD). Deep brain stimulation (DBS) of NAc has been identified as an effective treatment for severe refractory major depression; however, the underlying mechanism of NAc-DBS in MDD treatment remains elusive. Using the chronic unpredictable mild stress (CUMS) mouse model, we found NAc-DBS rescued depression-like behaviors, and reversed high gamma oscillation reduction and neurogenesis impairment in the dorsal dentate gyrus. Inactivation of parvalbumin (PV)-positive interneurons (PVI) in the dorsal DG led to depression-like behavior and decreased adult neurogenesis. Further investigation elucidated the VTA-DG GABAergic projection and CA1-NAc projection might jointly participate in NAc-DBS therapeutic mechanism. Disinhibition of the VTA-DG GABAergic projection had an antidepressant effect, and inhibition of the CA1-NAc projection reduced the antidepressant effect of DBS-NAc. Moreover, disinhibiting the VTA-DG GABAergic projection or activating the CA1-NAc projection could increase PVI activity in the dorsal DG. These results showed PVI in the dorsal DG as an essential target in depression and NAc-DBS antidepressant mechanisms.

Mu opioid receptor stimulation in the medial preoptic area or nucleus accumbens facilitates song and reward in flocking European starlings.

It has been proposed that social cohesion in gregarious animals is reinforced both by a positive affective state induced by social interactions and by the prevention of a negative state that would be caused by social separation. Opioids that bind to mu opioid receptors (MORs) act in numerous brain regions to induce positive and to reduce negative affective states. Here we explored a potential role for MORs in affective states that may impact flocking behavior in mixed-sex flocks of nonbreeding European starlings, Sturnus vulgaris. Singing behavior, which is considered central to flock cohesion, and other social behaviors were quantified after infusions of the MOR agonist D-Ala2, N-Me-Phe4, glycinol5-ENK (DAMGO) into either the medial preoptic area (POM) or the nucleus accumbens (NAC), regions previously implicated in affective state and flock cohesion. We focused on beak wiping, a potential sign of stress or redirected aggression in this species, to provide insight into a presumed negative state. We also used conditioned place preference (CPP) tests to provide insight into the extent to which infusions of DAMGO into POM or NAC that stimulated song might be rewarding. We found that MOR stimulation in either POM or NAC dose-dependently promoted singing behavior, reduced beak wiping, and induced a CPP. Subtle differences in responses to MOR stimulation between NAC and POM also suggest potential functional differences in the roles of these two regions. Finally, because the location of NAC has only recently been identified in songbirds, we additionally performed a tract tracing study that confirmed the presence of dopaminergic projections from the ventral tegmental area to NAC, suggesting homology with mammalian NAC. These findings support the possibility that MORs in POM and NAC play a dual role in reinforcing social cohesion in flocks by facilitating positive and reducing negative affective states.

μ-Opioid Receptor Stimulation in the Nucleus Accumbens Increases Vocal-Social Interactions in Flocking European Starlings, Sturnus Vulgaris.

Social connections in gregarious species are vital for safety and survival. For these reasons, many bird species form large flocks outside the breeding season. It has been proposed that such large social groups may be maintained via reward induced by positive interactions with conspecifics and via the reduction of a negative affective state caused by social separation. Moreover, within a flock optimal social spacing between conspecifics is important, indicating that individuals may optimize spacing to be close but not too close to conspecifics. The μ-opioid receptors (MORs) in the nucleus accumbens (NAc) are well known for their role in both reward and the reduction of negative affective states, suggesting that MOR stimulation in NAc may play a critical role in flock cohesion. To begin to test this hypothesis, social and nonsocial behaviors were examined in male and female European starlings (Sturnus vulgaris) in nonbreeding flocks after intra-NAc infusion of saline and three doses of the selective MOR agonist d-Ala2-N-Me-Phe4-Glycol5-enkephalin (DAMGO). DAMGO in NAc dose-dependently increased singing behavior and facilitated social approaches while at the same time promoting displacements potentially used to maintain social spacing. These findings support the hypothesis that MORs in NAc promote social interactions important for group cohesion in nonsexual contexts and suggest the possibility that MORs in the NAc play a role in optimizing the pull of joining a flock with the push of potential agonistic encounters.

Galanin Receptor 2 Is Involved in Galanin-Induced Analgesic Effect by Activating PKC and CaMKII in the Nucleus Accumbens of Inflammatory Pain Rats.

It has been reported that galanin has an analgesic effect via activating galanin receptors (GALRs). This study focused on the involvement of GALR2 in the galanin-induced analgesic effect and its signaling mechanism in the nucleus accumbens (NAc) of inflammatory rats. Animal models were established through injecting carrageenan into the plantar of rats’ left hind paw. The results showed that GALR2 antagonist M871 weakened partially the galanin-induced increases in hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation in NAc of inflammatory rats. Moreover, the GALR2 agonist M1145 prolonged the HWL and HWT, while M871 blocked the M1145-induced increases in HWL and HWT. Western blotting showed that the phosphorylation of calcium/calmodulin-dependent protein kinase II (p-CaMKII) and protein kinase C (p-PKC) in NAc were upregulated after carrageenan injection, while p-PKC and p-CaMKII were downregulated after intra-NAc administration of M871. Furthermore, the CaMKII inhibitor KN93 and PKC inhibitor GO6983 attenuated M1145-induced increases in HWL and HWT in NAc of rats with inflammatory pain. These results prove that GALR2 is involved in the galanin-induced analgesic effect by activating CaMKII and PKC in NAc of inflammatory pain rats, implying that GALR2 agonists probably are potent therapeutic options for inflammatory pain.

Nucleus Accumbens Stimulation Modulates Inhibitory Control by Right Prefrontal Cortex Activation in Obsessive-Compulsive Disorder.

Inhibitory control is considered a compromised cognitive function in obsessive-compulsive (OCD) patients and likely linked to corticostriatal circuitry disturbances. Here, 9 refractory OCD patients treated with deep brain stimulation (DBS) were evaluated to address the dynamic modulations of large-scale cortical network activity involved in inhibitory control after nucleus accumbens (NAc) stimulation and their relationship with cortical thickness. A comparison of DBS "On/Off" states showed that patients committed fewer errors and exhibited increased intraindividual reaction time variability, resulting in improved goal maintenance abilities and proactive inhibitory control. Visual P3 event-related potentials showed increased amplitudes during Go/NoGo performance. Go and NoGo responses increased cortical activation mainly over the right inferior frontal gyrus and medial frontal gyrus, respectively. Moreover, increased cortical activation in these areas was equally associated with a higher cortical thickness within the prefrontal cortex. These results highlight the critical role of NAc DBS for preferentially modulating the neuronal activity underlying sustained speed responses and inhibitory control in OCD patients and show that it is triggered by reorganizing brain functions to the right prefrontal regions, which may depend on the underlying cortical thinning. Our findings provide updated structural and functional evidence that supports critical dopaminergic-mediated frontal-striatal network interactions in OCD.

The orexinergic neural pathway from the lateral hypothalamus to the nucleus accumbens and its regulation of palatable food intake

ObjectiveTo explore the orexinergic pathway from the lateral hypothalamus (LHA) to the nucleus accumbens (NAc) and its regulation on the palatable food intake. MethodsFluorescent gold retrograde tracing combined with fluoro-immunohistochemical staining were used to observe the projection of orexinergic neurons from LHA to NAc. The orexin-A expression in LHA and c-Fos in NAc were studied after electrical stimulation of LHA. The firing rates of neurons were monitored by single-unit extracellular electric discharge recording and the palatable food intake were measured after orexin microinjection in NAc or electrical stimulation of LHA. Results(1) Fluorescent gold retrograde tracing combined with fluoro-immunohistochemical staining showed some orexinergic neural projection from the LHA to the NAc shell. (2) Electrical stimulation of LHA significantly enhanced the expression of orexin-A in LHA and the expression of c-Fos in NAc (P < .05). (3) The results of single-unit extracellular discharge recording showed that the microinjection of orexin in NAc or electrical stimulation of LHA significantly increased the discharge activity of gastric distension responsive neurons in NAc, and the effect could be partly blocked by pretreatment of orexin-A receptor inhibitor SB334867 in NAc (P < .05). (4) Microinjection orexin-A in NAc or electrical stimulation of LHA significantly increased the palatable food intake in rats, and the effect also was partly inhibited by pretreatment of SB334867 in NAc (P < .05). ConclusionThere is an orexinergic pathway from LHA to NAc, which may have potential regulatory effects on food reward and obesity.

Zona incerta projection neurons and GABAergic and GLP-1 mechanisms in the nucleus accumbens are involved in the control of gastric function and food intake

ObjectiveOur aim was to explore the effect of γ-aminobutyric acid (GABA) signaling in the nucleus accumbens (NAc) on promoting gastric function and food intake through glucagon-like peptide 1 (GLP-1)-sensitive gastric distension (GD) neurons under the regulatory control of the zona incerta (ZI). MethodsGABA neuronal projections were traced using retrograde tracing following fluorescence immunohistochemistry. An extracellular electrophysiological recording method was used to observe the firing of neurons in the NAc. HPLC was used to quantify the GABA and glutamate levels in the NAc after electrical stimulation of the ZI. Gastric functions including gastric motility and secretion, as well as food intake, were measured after the administration of different concentrations of GABA in the NAc or electrical stimulation of the ZI. ResultsSome of the GABA-positive neurons arising from the ZI projected to the NAc. Some GABA-A receptor (GABA-AR)-immunoreactive neurons in the NAc were also positive for GLP-1 receptor (GLP-1R) immunoreactivity. The firing of most GLP-1-sensitive GD neurons was decreased by GABA infusion in the NAc. Intra-NAc GABA administration also promoted gastric function and food intake. The responses induced by GABA were partially blocked by the GABA-AR antagonist bicuculline (BIC) and weakened by the GLP-1R antagonist exendin 9–39 (Ex9). Electrical stimulation of the ZI changed the firing patterns of most GLP-1-sensitive GD neurons in the NAc and promoted gastric function and food intake. Furthermore, these excitatory effects induced by electrical stimulation of the ZI were weakened by preadministration of BIC in the NAc. ConclusionRetrograde tracing and immunohistochemical staining showed a GABAergic pathway from the ZI to the NAc. GABAergic and GLP-1 mechanisms in the NAc are involved in the control of gastric function and food intake. In addition, the interaction (direct or indirect) between the ZI and these NAc mechanisms is involved in the control of gastric function and food intake.

The Effect of High-Frequency Electrical Stimulation of Bilateral Nucleus Accumbens on the Behavior of Morphine-Induced Conditioned Place Preference Rats at Extinction and Reinstatement Phases.

Objective To explore the optimal time points for deep brain stimulation (DBS) on the treatment of morphine addiction and its possible mechanisms by investigating how high-frequency stimulation (HFS) in bilateral nucleus accumbens (NAc) at different time points influences the addictive behaviors of rats with drug addiction. Methods The rats were randomly divided into extinction stimulation group (n = 20) and postextinction stimulation group (n = 20). Ten rats in the extinction stimulation group were treated using 120 Hz HFS during extinction stage while another 10 rats with pseudostimulation were served as control group. The CPP scores were evaluated at the second day after intervention, with total 9 sections accomplished. The CPP scores were evaluated at the second day of the intervention. In the postextinction stimulation group, 120 Hz HFS was intervened during the postextinction stage in 10 experimental rats and pseudostimulation was performed in 10 control rats. Stimulation was performed for 7 days continuously, and a small dose of morphine was administrated to induce relapse after the postextinction period. Results During the extinction phase, CPP scores after HFS were significantly higher. During the postextinction phase, relapse CPP scores after HFS were dramatically lower. Conclusion HFS of bilateral NAc inhibits the extinction of addictive behavior during the extinction phase, and HFS during the postextinction period suppresses relapse of drug seeking behavior.

Resting-state functional connectivity modulates the BOLD activation induced by nucleus accumbens stimulation in the swine brain.

IntroductionWhile the clinical efficacy of deep brain stimulation (DBS) the treatment of motor‐related symptoms is well established, the mechanism of action of the resulting cognitive and behavioral effects has been elusive.MethodsBy combining functional magnetic resonance imaging (fMRI) and DBS, we investigated the pattern of blood‐oxygenation‐level‐dependent (BOLD) signal changes induced by stimulating the nucleus accumbens in a large animal model.ResultsWe found that diffused BOLD activation across multiple functional networks, including the prefrontal, limbic, and thalamic regions during the stimulation, resulted in a significant change in inter‐regional functional connectivity. More importantly, the magnitude of the modulation was closely related to the strength of the inter‐regional resting‐state functional connectivity.ConclusionsNucleus accumbens stimulation affects the functional activity in networks that underlie cognition and behavior. Our study provides an insight into the nature of the functional connectivity, which mediates activation effect via brain networks.

Long-term results after deep brain stimulation of nucleus accumbens and the anterior limb of the internal capsule for preventing heroin relapse: An open-label pilot study

BackgroundDeep brain stimulation (DBS) is currently used to treat addiction, with the nucleus accumbens (NAc) as one promising target. The anterior limb of the internal capsule (ALIC) is also a potential target, as it carries fiber tracts connecting the mesocorticolimbic circuits that are crucially involved in several psychiatric disorders, including addiction. Stimulating the NAc and ALIC simultaneously may have a synergistic effect against addiction. MethodsEight patients with a long history of heroin use and multiple relapses, despite optimal conventional treatments, were enrolled. Customized electrodes were implanted through the ALIC into the NAc, and deep brain stimulation (DBS) treatment began two weeks after surgery. The patients were followed for at least 24 months. The duration of drug-free time, severity of drug cravings, psychometric evaluations, and PET studies of glucose metabolism before and after DBS were conducted. All adverse events were recorded. ResultsWith DBS, five patients were abstinent for more than three years, two relapsed after abstaining for six months, and one was lost of follow-up at three months. The degree of cravings for drug use after DBS was reduced if the patients remained abstinent (p < 0.001). Simultaneous DBS of the NAc and ALIC also improved the quality of life, alleviated psychiatric symptoms, and increased glucose metabolism in addiction-related brain regions. Moreover, stimulation-related adverse events were few and reversible. ConclusionsSimultaneous DBS of the NAc and ALIC appears to be safe, with few side effects, and may prevent long-term heroin relapse after detoxification in certain patients. (This trial was registered at ClinicalTrials.gov, NCT01274988).

Generalized seizures evoked by nucleus accumbens stimulation induced an opiate-mediated suppression of psychosis relevant behaviors

We have previously demonstrated that kindling of the nucleus accumbens (NAc) induced psychosis relevant behaviors only after one, but not after five, stage-5 seizures, suggesting that five stage-5 NAc-evoked seizures antagonized psychosis relevant behaviors in rats. We hypothesized that brain opioid receptors are responsible for seizure-induced reduction of psychosis relevant behaviors in NAc kindled rats. Rats received NAc kindling until a stage-4 seizure was induced, after which naloxone, a non-specific opioid receptor antagonist, at dose of 1 or 10 mg/kg i.p., or saline (0.3 mL) i.p., was injected 15 min before each kindled seizure. Duration of afterdischarge (AD) was not significantly different among naloxone- and saline-treated groups. However, duration of postictal behavioral depression induced by a stage-5 seizure was significantly shorter in 10 mg/kg naloxone-treated than saline-treated rats, for long (>36 s) AD duration. When tested 3–4 days after five stage-5 seizures, 10 mg/kg naloxone-treated rats, as compared to saline-treated rats, showed a statistically significant loss of gating of hippocampal auditory evoked potentials, and significant reduction of startle response amplitude, but non-significant differences in prepulse inhibition and methamphetamine-induced locomotion. It is inferred that stage-5 seizures, by releasing endogenous opiates, contribute to postictal behavioral depression, and some long-term seizure-induced antipsychotic effects.

In Reply to “Deep Brain Stimulation of Nucleus Accumbens: High Hopes for Simulating Orgasm in Spinal Cord Injury Patients”

In Reply to “Deep Brain Stimulation of Nucleus Accumbens: High Hopes for Simulating Orgasm in Spinal Cord Injury Patients”

Deep Brain Stimulation of Nucleus Accumbens: High Hopes for Simulating Orgasm in Spinal Cord Injury Patients

Deep Brain Stimulation of Nucleus Accumbens: High Hopes for Simulating Orgasm in Spinal Cord Injury Patients