Midbrain dopamine neurons arbiter OCD-like behavior.

The neurobiological understanding of obsessive-compulsive disorder (OCD) includes dysregulated frontostriatal circuitry and altered monoamine transmission. Repetitive stereotyped behavior (e.g., grooming), a featured symptom in OCD, has been proposed to be associated with perturbed dopamine (DA) signaling. However, the precise brain circuits participating in DA's control over this behavioral phenotype remain elusive. Here, we identified that DA neurons in substantia nigra pars compacta (SNc) orchestrate ventromedial striatum (VMS) microcircuits as well as lateral orbitofrontal cortex (lOFC) during self-grooming behavior. SNc-VMS and SNc-lOFC dopaminergic projections modulate grooming behaviors and striatal microcircuit function differentially. Specifically, the activity of the SNc-VMS pathway promotes grooming via D1 receptors, whereas the activity of the SNc-lOFC pathway suppresses grooming via D2 receptors. SNc DA neuron activity thus controls the OCD-like behaviors via both striatal and cortical projections as dual gating. These results support both pharmacological and brain-stimulation treatments for OCD.

Computational markers of risky decision-making predict for relapse to alcohol.

BACKGROUND: Relapse remains the major challenge in treatment of alcohol use disorder (AUD). Aberrant decision-making has been found as important cognitive mechanism underlying relapse, but factors associated with relapse vulnerability are unclear. Here, we aim to identify potential computational markers of relapse vulnerability by investigating risky decision-making in individuals with AUD. METHODS: Forty-six healthy controls and fifty-two individuals with AUD were recruited for this study. The risk-taking propensity of these subjects was investigated using the balloon analog risk task (BART). After completion of clinical treatment, all individuals with AUD were followed up and divided into a non-relapse AUD group and a relapse AUD group according to their drinking status. RESULTS: The risk-taking propensity differed significantly among healthy controls, the non-relapse AUD group, and the relapse AUD group, and was negatively associated with the duration of abstinence in individuals with AUD. Logistic regression models showed that risk-taking propensity, as measured by the computational model, was a valid predictor of alcohol relapse, and higher risk-taking propensity was associated with greater risk of relapse to drink. CONCLUSION: Our study presents new insights into risk-taking measurement and identifies computational markers that provide prospective information for relapse to drink in individuals with AUD.

Multiple mediation of the association between childhood emotional abuse and adult obesity by anxiety and bulimia - a sample from bariatric surgery candidates and healthy controls.

Bulimia, which means a person has episodes of eating a very large amount of food (bingeing) during which the person feels a loss of control over their eating, is the most primitive reason for being overweight and obese. The extended literature has indicated that childhood emotional abuse has a close relationship with adverse mood states, bulimia, and obesity. To comprehensively understand the potential links among these factors, we evaluated a multiple mediation model in which anxiety/depression and bulimia were mediators between childhood emotional abuse and body mass index (BMI). A set of self-report questionnaires, including the Childhood Trauma Questionnaire (CTQ), Beck Anxiety Inventory, Beck Depression Inventory (BDI), and Eating Disorder Inventory (EDI), was sent out. Clinical data from 37 obese patients (age: 29.65 ± 5.35, body mass index (BMI): 37.59 ± 6.34) and 37 demographically well-matched healthy people with normal body weight (age: 31.35 ± 10.84, BMI: 22.16 ± 3.69) were included in the investigation. We first performed an independent t-test to compare all scales or subscale scores between the two groups. Then, we conducted Pearson correlation analysis to test every two variables' pairwise correlation. Finally, multiple mediation analysis was performed with BMI as the outcome variable, and childhood emotional abuse as the predictive variable. Pairs of anxiety, bulimia, and depression, bulimia were selected as the mediating variables in different multiple mediation models separately. The results show that the obese group reported higher childhood emotional abuse (t = 2.157, p = 0.034), worse mood state (anxiety: t = 5.466, p < 0.001; depression: t = 2.220, p = 0.030), and higher bulimia (t = 3.400, p = 0.001) than the healthy control group. Positive correlations were found in every pairwise combination of BMI, childhood emotional abuse, anxiety, and bulimia. Multiple mediation analyses indicate that childhood emotional abuse is positively linked to BMI (ß = 1.312, 95% CI = 0.482-2.141). The model using anxiety and bulimia as the multiple mediating variables is attested to play roles in the relationship between childhood emotional abuse and obesity (indirect effect = 0.739, 95% CI = 0.261-1.608, 56.33% of the total effect). These findings confirm that childhood emotional abuse contributes to adulthood obesity through the multiple mediating effects of anxiety and bulimia. The present study adds another potential model to facilitate our understanding of the eating psychopathology of obesity.

Predictors of Electroconvulsive Therapy Outcome in Major Depressive Disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective therapy for major depressive disorder (MDD) patients. However, few clinical predictors are available to predict the treatment outcome. This study aimed to characterize the response trajectories of MDD patients undergoing ECT treatment and to identify potential clinical and demographic predictors for clinical improvement. METHODS: We performed a secondary analysis on data from a multicenter, randomized, blinded, controlled trial with 3 ECT modalities (bifrontal, bitemporal, unilateral). The sample consisted of 239 patients whose demographic and clinical characteristics were investigated as predictors of ECT outcomes. RESULTS: The results of growth mixture modeling suggested there were 3 groups of MDD patients: a non-remit group (n = 17, 7.11%), a slow-response group (n = 182, 76.15%), and a rapid-response group (n = 40, 16.74%). Significant differences in age, education years, treatment protocol, types of medication used, Hamilton Depression Scale, Hamilton Anxiety Scale score, Mini-Mental State Examination score, and Clinical Global Impression score at baseline were observed across the groups. CONCLUSIONS: MDD patients exhibited distinct and clinically relevant response trajectories to ECT. The MDD patients with more severe depression at baseline are associated with a rapid response trajectory. In contrast, MDD patients with severe symptoms and older age are related to a less response trajectory. These clinical predictors may help guide treatment selection.

Intermittent theta burst stimulation to the left dorsolateral prefrontal cortex improves working memory of subjects with methamphetamine use disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation has been employed to treat drug dependence, reduce drug use and improve cognition. The aim of the study was to analyze the effectiveness of intermittent theta-burst stimulation (iTBS) on cognition in individuals with methamphetamine use disorder (MUD). METHODS: This was a secondary analysis of 40 MUD subjects receiving left dorsolateral prefrontal cortex (L-DLPFC) iTBS or sham iTBS for 20 times over 10 days (twice-daily). Changes in working memory (WM) accuracy, reaction time, and sensitivity index were analyzed before and after active and sham rTMS treatment. Resting-state EEG was also acquired to identify potential biological changes that may relate to any cognitive improvement. RESULTS: The results showed that iTBS increased WM accuracy and discrimination ability, and improved reaction time relative to sham iTBS. iTBS also reduced resting-state delta power over the left prefrontal region. This reduction in resting-state delta power correlated with the changes in WM. CONCLUSIONS: Prefrontal iTBS may enhance WM performance in MUD subjects. iTBS induced resting EEG changes raising the possibility that such findings may represent a biological target of iTBS treatment response.

Celsr2 regulates NMDA receptors and dendritic homeostasis in dorsal CA1 to enable social memory.

Social recognition and memory are critical for survival. The hippocampus serves as a central neural substrate underlying the dynamic coding and transmission of social information. Yet the molecular mechanisms regulating social memory integrity in hippocampus remain unelucidated. Here we report unexpected roles of Celsr2, an atypical cadherin, in regulating hippocampal synaptic plasticity and social memory in mice. Celsr2-deficient mice exhibited defective social memory, with rather intact levels of sociability. In vivo fiber photometry recordings disclosed decreased neural activity of dorsal CA1 pyramidal neuron in Celsr2 mutants performing social memory task. Celsr2 deficiency led to selective impairment in NMDAR but not AMPAR-mediated synaptic transmission, and to neuronal hypoactivity in dorsal CA1. Those activity changes were accompanied with exuberant apical dendrites and immaturity of spines of CA1 pyramidal neurons. Strikingly, knockdown of Celsr2 in adult hippocampus recapitulated the behavioral and cellular changes observed in knockout mice. Restoring NMDAR transmission or CA1 neuronal activities rescued social memory deficits. Collectively, these results show a critical role of Celsr2 in orchestrating dorsal hippocampal NMDAR function, dendritic and spine homeostasis, and social memory in adulthood.

Growth charts of brain morphometry for preschool children.

Brain development from 1 to 6 years of age anchors a wide range of functional capabilities and carries early signs of neurodevelopmental disorders. However, quantitative models for depicting brain morphology changes and making individualized inferences are lacking, preventing the identification of early brain atypicality during this period. With a sample size of 285, we characterized the age dependence of the cortical thickness and subcortical volume in neurologically normal children and constructed quantitative growth charts of all brain regions for preschool children. While the cortical thickness of most brain regions decreased with age, the entorhinal and parahippocampal regions displayed an inverted-U shape of age dependence. Compared to the cortical thickness, the normalized volume of subcortical regions exhibited more divergent trends, with some regions increasing, some decreasing, and some displaying inverted-U-shaped trends. The growth curve models for all brain regions demonstrated utilities in identifying brain atypicality. The percentile measures derived from the growth curves facilitate the identification of children with developmental speech and language disorders with an accuracy of 0.875 (area under the receiver operating characteristic curve: 0.943). Our results fill the knowledge gap in brain morphometrics in a critical development period and provide an avenue for individualized brain developmental status evaluation with demonstrated sensitivity. The brain growth charts are shared with the public (http://phi-group.top/resources.html).

Predictable maternal separation confers adult stress resilience via the medial prefrontal cortex oxytocin signaling pathway in rats.

Early-life stress is normally thought of as a major risk for psychiatric disorders, but many researchers have revealed that adversity early in life may enhance stress resilience later in life. Few studies have been performed in rodents to address the possibility that exposure to early-life stress may enhance stress resilience, and the underlying neural mechanisms are far from being understood. Here, we established a "two-hit" stress model in rats by applying two different early-life stress paradigms: predictable and unpredictable maternal separation (MS). Predictable MS during the postnatal period promotes resilience to adult restraint stress, while unpredictable MS increases stress susceptibility. We demonstrate that structural and functional impairments occur in glutamatergic synapses in pyramidal neurons of the medial prefrontal cortex (mPFC) in rats with unpredictable MS but not in rats with predictable MS. Then, we used differentially expressed gene (DEG) analysis of RNA sequencing data from the adult male PFC to identify a hub gene that is responsible for stress resilience. Oxytocin, a peptide hormone, was the highest ranked differentially expressed gene of these altered genes. Predictable MS increases the expression of oxytocin in the mPFC compared to normal raised and unpredictable MS rats. Conditional knockout of the oxytocin receptor in the mPFC was sufficient to generate excitatory synaptic dysfunction and anxiety behavior in rats with predictable MS, whereas restoration of oxytocin receptor expression in the mPFC modified excitatory synaptic function and anxiety behavior in rats subjected to unpredictable MS. These findings were further supported by the demonstration that blocking oxytocinergic projections from the paraventricular nucleus of the hypothalamus (PVN) to the mPFC was sufficient to exacerbate anxiety behavior in rats exposed to predictable MS. Our findings provide direct evidence for the notion that predictable MS promotes stress resilience, while unpredictable MS increases stress susceptibility via mPFC oxytocin signaling in rats.

Neurophysiological correlate of incubation of craving in individuals with methamphetamine use disorder.

Previous studies both in laboratory animals and humans have reported that abstinence induces incubation of cue-induced drug craving for nicotine, alcohol, cocaine, and methamphetamine. However, current experimental procedures utilized to study incubation of methamphetamine craving do not incorporate the temporal dynamics of neuropsychological measures and electrophysiological activities associated with this incubation process. This study utilized the high-density electroencephalogram (EEG) signals as a rapid, inexpensive, and noninvasive measure of cue-induced craving potential. A total of 156 male individuals with methamphetamine use disorder (MUD) enrolled in this multisite, cross-sectional study. Structured clinical interview data, self-report questionnaires (cued craving, quality of sleep, impulsivity, anxiety, and depression) and resting-state, eye-closed 128 high-density channel EEG signals were collected at 5 abstinence duration time points (<1, 1-3, 3-6, 6-12, and 12-24 months) to track the neuropsychological and neurophysiological signatures. Cue-induced craving was higher after 1-3 months than after the other time points. This incubation effect was also observed for sleep quality but not for anxiety, depression, and impulsivity symptoms, along with exhibited decreased power spectrum for theta (5.5-8 Hz) and alpha (8-13 Hz), and increased in beta (16.5-26.5 Hz) frequency band. Source reconstructed resting-state EEG analysis showed increased synchronization of medial prefrontal cortex (MPFC) for the beta frequency band in 1-3 months abstinent MUD group, and associated with the incubation of craving. Remarkably, the robust incubation-related abnormalities may be driven by beta-band source space connectivity between MPFC and bilateral orbital gyrus (ORB). Our findings suggest the enhancement of beta activity in the incubation period most likely originates from a dysfunction involving frontal brain regions. This neurophysiological signature of incubation of craving can be used to identify individuals who might be most susceptible to relapse, providing a potential insight into future therapeutic interventions for MUD via neuromodulation of beta activity.

Physical exercise rescues cocaine-evoked synaptic deficits in motor cortex.

Drug exposure impairs cortical plasticity and motor learning, which underlies the reduced behavioral flexibility in drug addiction. Physical exercise has been used to prevent relapse in drug rehabilitation program. However, the potential benefits and molecular mechanisms of physical exercise on drug-evoked motor-cortical dysfunctions are unknown. Here we report that 1-week treadmill training restores cocaine-induced synaptic deficits, in the form of improved in vivo spine formation, synaptic transmission, and spontaneous activities of cortical pyramidal neurons, as well as motor-learning ability. The synaptic and behavioral benefits relied on de novo protein synthesis, which are directed by the activation of the mechanistic target of rapamycin (mTOR)-ribosomal protein S6 pathway. These findings establish synaptic functional restoration and mTOR signaling as the critical mechanism supporting physical exercise training in rehabilitating the addicted brain.

Reduced motor cortex GABABR function following chronic alcohol exposure.

The GABAB receptor (GABABR) agonist baclofen has been used to treat alcohol and several other substance use disorders (AUD/SUD), yet its underlying neural mechanism remains unclear. The present study aimed to investigate cortical GABABR dynamics following chronic alcohol exposure. Ex vivo brain slice recordings from mice chronically exposed to alcohol revealed a reduction in GABABR-mediated currents, as well as a decrease of GABAB1/2R and G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) activities in the motor cortex. Moreover, our data indicated that these alterations could be attributed to dephosphorylation at the site of serine 783 (ser-783) in GABAB2 subunit, which regulates the surface expression of GABABR. Furthermore, a human study using paired-pulse-transcranial magnetic stimulation (TMS) analysis further demonstrated a reduced cortical inhibition mediated by GABABR in patients with AUD. Our findings provide the first evidence that chronic alcohol exposure is associated with significantly impaired cortical GABABR function. The ability to promote GABABR signaling may account for the therapeutic efficacy of baclofen in AUD.

Lateral septum inputs to nucleus accumbens mediates stress induced suppression of natural reward seeking.

Stress alters the level of reward evaluation and seeking. However, the neural circuitry mechanisms underlying stress induced effects on natural reward seeking remain unclear. Here we report a septal-accumbens pathway that mediates the effects of acute stress on reward seeking suppression. We first established the sucrose oral self-administration paradigm and measured the effects of acute stress on reward seeking behavior after 21 days of abstinence. Both forced swimming stress and foot shock stress significantly suppressed the natural reward seeking. Among a variety of brain regions, intermediolateral septum (LSi) appear as a strong stress-responsive area containing abundant c-Fos positive cells; chemogenetic inactivation of LSi reinstated the reward seeking behavior. To elucidate the downstream targets receiving LSi projections, we combined pathway-specific retro-labeling and chemogenetic manipulation to confirm the involvement of LSi-nucleus accumbens (NAc) rather than the Ventral tegmental area (VTA) in mediating the observed behavioral responses. In conclusion, the septal-accumbal projection constitute a discrete circuit dictating the stress evoked alterations on reward seeking and may implicate in treatment of stress induced anhedonia.

Impaired delay discounting and time sensitivity in methcathinone use disorder.

Substance use disorder (SUD) is characterized by continued drug use despite adverse consequences. Methcathinone is a new type of psychoactive substance that is associated with high excitement and impulsive behaviors. However, it is unclear if individuals with methcathinone use disorders (MCUD) are with impaired decision-making ability. We analyzed the task performance in 45 male MCUD subjects and 35 male matched healthy controls (HC) with intertemporal decision-making task. Constant sensitivity discounting model was used to estimate potential changes in both discounting rate and time sensitivity. The results showed that MCUD individuals exhibited a higher delay discounting rate (p = 0.003, Cohen's d = 0.683) and reduced sensitivity to time (p < 0.001, Cohen's d = 1.662). The delay discounting rate was correlated to the first age for drug use (r = - 0.41, p = 0.004), and the time sensitivity was negatively correlated with the duration of abstinence (r = - 0.31, p = 0.036). We conclude that MCUD individuals are with impaired decision-making ability and time perception disturbances.

Time-dependent affective disturbances in abstinent patients with methylphenidate use disorder.

BACKGROUND: Methylphenidate (MPH), also called Ritalin, is used to treat attention-deficit hyperactivity disorder (ADHD) patients. With occasional reports of subjects suffering from Methylphenidate use disorder (MPHUD), few studies analyzed the neuropsychological changes in this population. PURPOSE: This study aims to evaluate the clinical outcomes of individuals with MPHUD. METHODS: We retrospectively analyzed 61 MPH patients (aged 16-27 years) admitted to the Beijing Gaoxin Hospital drug rehabilitation program from Jan 2017 to Mar 2019. The drug use history and drug abuse motivation scale were collected at admission. Clinicians rated the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and DSM-5 Stimulant use disorder criteria each week during the 4 weeks rehabilitation program. Correlation analyses were conducted between drug use history and affective disturbances. RESULTS: The results showed that the adolescent period is the peak for MPH exposure, and 1/3 of patients got their first exposure to MPH from their parents. MPH abstinence accompanies severe anxiety and depression symptoms, significantly alleviating after four weeks of treatment. CONCLUSIONS: MPHUD is associated with substantial affective disturbances, which warrants a more considerable sample investigation.

Impaired social decision-making in males with methamphetamine use disorder.

Individuals with methamphetamine use disorder (MUD) commonly exhibit socially problematic behaviours. Investigating the prosocial decision-making of individuals with MUD could enable a better understanding of their impaired social functioning and help improve their social relationships. We conducted two studies to examine the performance of individuals with MUD and healthy controls on a modified dictator game. In Study 1, 55 male individuals with MUD and 34 healthy male participants made a series of choices between two pairs of monetary prizes for themselves and for others. In Study 2, 62 male individuals with MUD and 31 healthy male participants made the same choices as in Study 1 after a brief exposure to methamphetamine-related pictures. In both studies, we consistently found a context dependency of decreased prosociality in individuals with MUD. That is, individuals with MUD made fewer prosocial choices than healthy individuals in disadvantageous contexts (but not advantageous contexts). The results of the computational model suggested that the lower prosociality of individuals with MUD in disadvantageous contexts could be attributed to the lower weight placed on others' benefits. Moreover, when exposed to methamphetamine-related pictures, individuals with MUD showed less caution and slower encoding/motor speed than healthy individuals, and individuals with MUD with a longer history of methamphetamine use tended to respond less cautiously. Our findings provide evidence that in disadvantageous contexts, individuals with MUD show reduced prosociality and less consideration of others' benefits. Identifying the origin of the alterations in prosocial decision-making has implications for diagnosis and treatment.

Probing drug-evoked cortical plasticity with brain stimulation: A call for translation from animal to human medical research.

Drug evoked synaptic plasticity represents "memory traces" in the brain following abuse experiences. Preclinical studies have detailed the myriad changes in mesolimbic and cortical functioning, including alterations in synaptic transmission and plasticity. In humans, recent research advances utilizing a combination of non-invasive brain stimulation and neurophysiological readouts have opened a new avenue for the study cortical plasticity in clinical substance dependence states. These insights, along with findings in psychopathology more generally, uniquely positions brain stimulation as a key tool for understanding cortical function and plasticity in substance dependence.

Color painting predicts clinical symptoms in chronic schizophrenia patients via deep learning.

BACKGROUND: Individuals with psychiatric disorders perceive the world differently. Previous studies indicated impaired color vision and weakened color discrimination ability in psychotic patients. Examining the paintings from psychotic patients can measure the visual-motor function. However, few studies examined the potential changes in the color painting behavior in these individuals. The current study aims to discriminate schizophrenia patients from healthy controls (HCs) and predict PANSS scores of schizophrenia patients according to their paintings. METHODS: In the present study, we retrospectively analyzed the paintings colored by 281 chronic schizophrenia patients and 35 HCs. The images were scanned and processed using series of computational analyses. RESULTS: The results showed that schizophrenia patients tend to use less color and exhibit different strokes compared to HCs. Using a deep learning residual neural network (ResNet), we were able to discriminate patients from HCs with over 90% accuracy. Further, we developed a novel convolutional neural network to predict PANSS positive, negative, general psychopathology, and total scores. The Root Mean Square Error (RMSE) of the prediction was low, which indicates higher accuracy of prediction. CONCLUSION: In conclusion, the deep learning paradigm showed the large potential to discriminate schizophrenia patients from HCs based on color paintings. Besides, this color painting-based paradigm can effectively predict clinical symptom severity for chronic schizophrenia patients. The color paintings by schizophrenia patients show potential as a tool for clinical diagnosis and prognosis. These findings show potential as a tool for clinical diagnosis and prognosis among schizophrenia patients.

Brief Report: Predictors of Relapse for Patients With Dextromethorphan Dependence.

BACKGROUND AND OBJECTIVES: The recreational use of dextromethorphan (DXM) triggers dependence. The pattern and clinical predictors of relapse are unclear. METHODS: Here, we retrospectively analyzed the clinical information of 28 patients with DXM dependence (20 males and 8 females). RESULTS: The mean age at admission was 25.89 years (standard deviation [SD] = 7.84), and the average duration of DXM abuse was 24.96 months (SD = 17.40). The relapse rates at 1 month, 3 months, 6 months, and 1 year were 7.14%, 25%, 71.43%, and 89.29%, respectively. Depression and anxiety status at baseline were positive predictors of relapse (r = -.539, P = .006, R2 = 0.290; r = -.449, P = .024, R2 = 0.202, respectively). DISCUSSION AND CONCLUSIONS: Our results suggest that patients with DXM dependence are at high risk of relapse and that measuring affective disturbance is important for predicting the outcomes of their treatment. SCIENTIFIC SIGNIFICANCE: This study first identified a high relapse rate among patients with DXM dependence and found that the baseline depression and anxiety status was correlated with the time length of relapse. These findings not only warn us of the vulnerability of DXM-dependent relapse but also reveal the importance of measuring affective disturbance in relapse prevention. (Am J Addict 2020;00:00-00).

Adolescent cocaine exposure enhances the GABAergic transmission in the prelimbic cortex of adult mice.

We have recently shown in rats that adolescent cocaine exposure induces prolonged modifications on synapses in medial prefrontal cortex (mPFC), which might contribute to long-term behavioral outcomes in adulthood. In this study, we further investigated the molecular mechanisms underlying adolescent cocaine exposure-related psychiatric problems in adulthood, especially focusing on the alterations of GABAergic transmission in prelimbic cortex (PrL), 1 subregion of mPFC. Consistent with a previous study, adolescent cocaine-exposed mice exhibited enhanced anxiety-like behaviors in their adulthood. In the same mice models, depression-like behaviors increased as well, but the conditioned place preference formed normally. In parallel, activities of pyramidal neurons at layer V of PrL were reduced after adolescent cocaine exposure, accompanied by an increase in the percentage of symmetric synapses in PrL of adult mice. Additionally, miniature inhibitory postsynaptic currents rather than miniature excitatory postsynaptic currents were increased on these pyramidal neurons, and increased levels of GABA were found in adult PrL. The molecules in the GABAergic system in adult PrL were also changed by adolescent cocaine use, as indicated by increased glutamate decarboxylase 67 kDa, GABAA-α1, and decreased GABA transporter 1. In the same mice, some regulators to GABAergic transmission such as neuregulin 1/ErbB4 signals were heightened as well. Collectively, these findings revealed that adolescent cocaine exposure results in permanent enhancement of GABAergic transmission on pyramidal neurons in PrL, which subsequently attenuate the activities of these neurons and ultimately contributes to the development of psychiatric disorders in later life.-Shi, P., Nie, J., Liu, H., Li, Y., Lu, X., Shen, X., Ge, F., Yuan, T.-F., Guan, X. Adolescent cocaine exposure enhances the GABAergic transmission in the prelimbic cortex of adult mice.

Fish oil treatment reduces chronic alcohol exposure induced synaptic changes.

Alcohol addiction is a chronic neuropsychiatric disorder that represents one of the most serious global public health problems. Yet, currently there still lacks an effective pharmacotherapy. Omega-3 polyunsaturated fatty acids (N-3 PUFAs) have exhibited beneficial effects in a variety of neurological disorders, particularly in reversing behavioral deficits and neurotoxicity induced by prenatal alcohol exposure and binge drinking. In the present study, we investigated if fish oil, which is rich in N-3 PUFAs, had beneficial effects on preventing relapse and alleviating withdrawal symptoms after chronic alcohol exposure. Our results demonstrated that fish oil significantly reduced the chronic alcohol exposure-induced aberrant dendritic morphologic changes of the medium-sized spiny neurons in the core and the shell of nucleus accumbens. This inhibited the expression of AMPAR2-lacking AMPARs and their accumulation on the post synaptic membranes of medium-sized spiny neurons and eventually alleviated withdrawal symptoms and alcohol dependence. Our study therefore suggests that N-3 PUFAs are promising for treating withdrawal symptoms and alcohol dependence.