Mesolimbic Dopaminergic System Research Articles

Behavioral changes and transcriptional regulation of mesolimbic dopaminergic genes in a mouse model of binge eating disorder by diet intermittent access.

Binge Eating Disorder (BED) is among the most prevalent eating disorders worldwide. It is characterized by recurrent episodes of excessive consumption of palatable foods in short periods, accompanied by a sense of loss of control and distress around the episode, which tends to worsen over time. The mesolimbic dopaminergic system influences on reinforcement and reward-seeking behaviors is implicated in the disorder's pathogenesis. Animal models that replicate the clinical conditions observed in humans, including the disorder progression, are essential for understanding the underlying physiological mechanisms of BED. This study aimed to evaluate binge eating behavior induced by intermittent High Sugar and Butter (HSB) diet access in mice, their phenotypes, transcriptional regulation of mesolimbic dopaminergic system genes, and behavior. Thus, mice were subdivided into three groups: CHOW (maintenance diet only), HSB-i (maintenance diet with thrice-weekly access to HSB), and HSB (continuous access to HSB). Animals were subjected to marble-burying and light-dark box behavioral tests, and transcriptional regulation was evaluated by RT-qPCR. The results indicated that the HSB-i group established a feeding pattern of significantly more kilocalories on days when HSB was available and reduced intake on non-HSB days similar to human binge eating. Over time, binge episodes intensified, potentially indicating a tolerance effect. Additionally, these animals behave differently towards preferring the HSB diet and exhibited altered transcriptional regulation of the Drd1, Slc6a3, and Lrrk2 genes. Our study provides a mouse model that reflects human BED, showing a progression in binge episodes and mesolimbic dopamine pathway involvement, suggesting targets for future therapeutic interventions.

From emotional arousal to executive action. Role of the prefrontal cortex.

Emotional arousal is caused by the activity of two parallel ascending systems targeting mostly the subcortical limbic regions and the prefrontal cortex. The aversive, negative arousal system is initiated by the activity of the mesolimbic cholinergic system and the hedonic, appetitive, arousal is initiated by the activity of the mesolimbic dopaminergic system. Both ascending projections have a diffused nature and arise from the rostral, tegmental part of the brain reticular activating system. The mesolimbic cholinergic system originates in the laterodorsal tegmental nucleus and the mesolimbic dopaminergic system in the ventral tegmental area. Cholinergic and dopaminergic arousal systems have converging input to the medial prefrontal cortex. The arousal system can modulate cortical EEG with alpha rhythms, which enhance synaptic strength as shown by an increase in long-term potentiation (LTP), whereas delta frequencies are associated with decreased arousal and a decrease in synaptic strength as shown by an increase in long-term depotentiation (LTD). It is postulated that the medial prefrontal cortex is an adaptable node with decision making capability and may control the switch between positive and negative affect and is responsible for modifying or changing emotional state and its expression.

Association Study of Serotonin 1A Receptor Gene, Personality, and Anxiety in Women with Alcohol Use Disorder.

Alcohol use disorder is considered a chronic and relapsing disorder affecting the central nervous system. The serotonergic system, mainly through its influence on the mesolimbic dopaminergic reward system, has been postulated to play a pivotal role in the underlying mechanism of alcohol dependence. The study aims to analyse the association of the rs6295 polymorphism of the 5HTR1A gene in women with alcohol use disorder and the association of personality traits with the development of alcohol dependence, as well as the interaction of the rs6295, personality traits, and anxiety with alcohol dependence in women. The study group consisted of 213 female volunteers: 101 with alcohol use disorder and 112 controls. NEO Five-Factor and State-Trait Anxiety Inventories were applied for psychometric testing. Genotyping of rs6295 was performed by real-time PCR. We did not observe significant differences in 5HTR1A rs6295 genotypes (p = 0.2709) or allele distribution (p = 0.4513). The AUD subjects scored higher on the anxiety trait (p < 0.0001) and anxiety state (p < 0.0001) scales, as well as on the neuroticism (p < 0.0001) and openness (p = 0134) scales. Significantly lower scores were obtained by the AUD subjects on the extraversion (p < 0.0001), agreeability (p < 0.0001), and conscientiousness (p < 0.0001) scales. Additionally, we observed a significant effect of 5HTR1A rs6295 genotype interaction and alcohol dependency, or lack thereof, on the openness scale (p = 0.0016). In summary, this study offers a comprehensive overview of alcohol dependence among women. It offers valuable insights into this complex topic, contributing to a more nuanced understanding of substance use among this specific demographic. Additionally, these findings may have implications for developing prevention and intervention strategies tailored to individual genetic and, most importantly, personality and anxiety differences.

Impact of Precision Nutrition on Microbiota and Obesity

Abstract: The human body is colonized by trillions of microbes, that contribute to our health and well-being. Many factors influence the composition and functions of the intestinal microbiota, including the host's eating habits, which seem to have a significant effect. A healthy intestinal microbiota is essential for proper metabolic function and homeostasis. Alterations in microbial composition could dramatically cause obesity and diabetes, modifying and influencing host metabolism, homeostasis, and central appetite mechanism. Brain reward signaling is mediated by the dopaminergic mesolimbic system and plays an important role in the development of obesity. Dysregulation of the energy balance causes obesity. Obesity is a serious health problem. The composition of the intestinal microbiota influences various aspects of energy metabolism: digestion, food intake from ingested foods, food components, and accumulation of excess fat. Therefore, the microbial community can contribute significantly to the progression of obesity and its complications. A "tailored nutritional approach" and more feasible and sustainable personalized nutritional strategies must be developed to optimize the gut microbiome and improve host response.

Response of nitrergic system in the brain of rat conditioned to intracranial self-stimulation.

The role of nitrergic system in modulating the action of psychostimulants on reward processing is well established. However, the relevant anatomical underpinnings and scope of the involved interactions with mesolimbic dopaminergic system have not been clarified. Using immunohistochemistry, we track the changes in neuronal nitric oxide synthase (nNOS) containing cell groups in the animals conditioned to intracranial self-stimulation (ICSS) via an electrode implanted in the lateral hypothalamus-medial forebrain bundle (LH-MFB) area. An increase in the nNOS immunoreactivity was noticed in the cells and fibers in the ventral tegmental area (VTA) and nucleus accumbens shell (AcbSh), the primary loci of the reward system. In addition, nNOS was up-regulated in the nucleus accumbens core (AcbC), vertical limb of diagonal band (VDB), locus coeruleus (LC), lateral hypothalamus (LH), superficial gray layer (SuG) of the superior colliculus, and periaqueductal gray (PAG). The brain tissue fragments drawn from these areas showed a change in nNOS mRNA expression, but in opposite direction. Intracerebroventricular (icv) administration of nNOS inhibitor, 7-nitroindazole (7-NI) showed decreased lever press activity in a dose-dependent manner in ICSS task. While an increase in the dopamine (DA) and 3, 4-dihydroxyphenylacetic acid (DOPAC) efflux was noted in the microdialysates collected from the AcbSh of ICSS rats, pre-administration of 7-NI (icv route) attenuated the response. The study identifies nitrergic centers that probably mediate sensory, cognitive, and motor components of the goal-directed behavior.

Selective orexin 1 receptor antagonism does not affect effort-based responding for sucrose reward in rats.

In rodents, orexin neuropeptides regulate motivation and reward-seeking via orexin 1 receptor (OX1R) signaling in the mesolimbic dopaminergic system. This role is clearly established for rewards inherent to drugs of abuse but less so for natural rewards. Reported effects of the selective OX1R antagonist (SO1RA) SB-334867 on motivation for palatable food are ambiguous. In our experimental conditions neither SB-334867, nor two additional, structurally different SO1RAs, ACT-335827 and the clinical development candidate nivasorexant, affected effort-based responding for sucrose in rats. The positive control lisdexamfetamine, approved for psychiatric disorders associated with altered reward sensitivity such as binge eating disorder, increased effort-based responding.

Evaluation of White Matter and Cerebellum Structures of Essential Tremor and Parkinson's Patients by Diffusion Tensor Imaging and Volbrain Method

Essential tremor (ET) and Parkinson's disease (PD) are the two most commonly encountered tremor disorders in movement disorders. Diffusion tensor imaging (DTI) is one of the best in vivo ways of mapping white matter pathways in the human brain. The aim of our study was to investigate diffusion variables and cerebellum volume in ET and PD using parcellation methods. Our study included 20 ET, 20 PD and 20 healthy controls. Fraction Anisotropy (FA) and Mean Diffusivity (MD) values were obtained with DTI, while the volume of each lobe of the cerebellum was obtained with T1 images. One-way ANOVA was used for intergroup analysis and Scheffe test was used for post-hoc analysis. Significant differences were found in the diffusion values of the pedunculus cerebellaris, fornix stria, superior longitudinal fasciculus, sagittal stratum, cerebral pedunculus, tapatum and thalamus of ET and PD. Lobule V, Lobule IX, Lobule X volumes of the cerebellum showed significant differences between the groups. Stria thermialis shows involvement of mesolimbic dopaminergic system in PD and it is thought that disruption of strial networks leads to changes in the activity of cerebellar networks and reveals the role of the cerebellum in tremor. It is obvious that cerebellar thalamocortical pathways are affected in Parkinson's disease. In Parkinson's disease, patients should be evaluated for visual processing, conceptualisation, postural instability and gait disturbance to clarify the diagnosis or to differentiate from essential tremor.

Adolescent alcohol and nicotine exposure alters the adult response to alcohol use.

Adolescence through young adulthood is a unique period of neuronal development and maturation. Numerous agents can alter this process, resulting in long-term neurological and biological consequences. In the clinical literature, it is frequently reported that adolescent alcohol consumption increases the propensity to develop addictions, including alcohol use disorder (AUD), during adulthood. A general limitation of both clinical and human pre-clinical adolescent alcohol research is the high rate of co-using/abusing more than one drug during adolescence, such as co-using/abusing alcohol with nicotine. A primary goal of basic research is elucidating neuroadaptations produced by adolescent alcohol exposure/consumption that promote alcohol and other drug self-administration in adulthood. The long-term goal is to develop pharmacotherapeutics for the prevention or amelioration of these neuroadaptations. This review will focus on studies that have examined the effects of adolescent alcohol and nicotine exposure on adult alcohol consumption, the hypersensitivity of the mesolimbic dopaminergic system, and enhanced responses not only to alcohol but also to nicotine during adulthood. Again, the long-term goal is to identify potential cholinergic agents to prevent or ameliorate the consequences of, peri-adolescent alcohol abuse.

The differential processing of verbal jokes by neural substrates in indigenous and Han Chinese populations: An fMRI study

Limited research has been conducted on humor among the Taiwanese indigenous (IND) population. This study attempted to identify the differential neural correlates of humor comprehension and appreciation between IND and Han Chinese (HAN) populations. Each participant was presented with jokes and non-jokes. IND participants when encountered with jokes displayed a greater activation of the mesolimbic dopaminergic reward system, including the amygdala, midbrain, and nucleus accumbens than HAN participants. This suggests a more pleasurable response and appreciation of humor. The IND group also displayed greater activation in the right temporoparietal junction (rTPJ) than HAN, suggesting that the IND group may experience a greater sense of novelty and be more involved in social understanding, thus exhibiting greater humor appreciation. In terms of humor comprehension, both IND and HAN showed greater activation in the superior temporal gyrus (STG) and dorsal anterior cingulate cortex (dACC). IND exhibited greater activation in the anterior STG (aSTG), while HAN showed greater activation in the posterior STG (pSTG). This suggests that the IND tends to integrate emotional messages, whereas the HAN focuses on comprehending semantic cognitive information. Interestingly, HAN did not show any greater activation than IND in terms of appreciation of humor. These group disparities have substantial implications for advancing our knowledge of the neural mechanisms underlying humor comprehension and appreciation.

Модуляція прогестероном тривожності та активності дофамінергічної мезолімбічної системи мозку у щурів з алкогольною залежністю і за умов зоосоціального конфлікту

Exogenous modulation by progesterone of the central neurosteroid mechanisms of regulation of anxiety and its important component, the activity of the mesolimbic dopaminergic system, is a promising method of correction of emotional behavioral disorders. The aim of this work was to study the effect of intranasal progesterone administration on the baseline level of anxiety and the activity of the dopaminergic mesolimbic brain system in alcohol-dependent and zoosocial conflict rats. Neuroethological studies by the method of assessing the individual level of anxiety. The levels of catecholamines (dopamine, noradrenaline, adrenaline) in the brain structures were determined by the method of immunoenzymatic analysis. Emotional stress, namely zoosocial instability and confrontational interactions, was modeled using the sensory contact technique and the partition test. Alcohol dependence in rats was induced by voluntary consumption of alcohol-containing food. Progesterone was administered intranasally at a dose of 80 μg per animal. It is shown that the level of anxiety in rats under conditions of alcohol dependence and emotional stress is associated with dopamine and adrenergic disturbances in the ventral tegmental area (VTA) and nucleus accumbens. The anxiolytic effects of progesterone are manifested in the suppression of the increase in anxiety following exposure to emotional stress in alcohol-dependent rats and its suppression in rats with baseline low levels of anxiety following repeated exposure to emotional stress. A balanced activation of the dopaminergic mesolimbic system during progesterone administration leads to the formation of a new allostatic state in rats with a decrease in anxiety levels.

Cortical theta oscillations and 50-kHz ultrasonic vocalizations in response to tactile reward indicate positive emotion in rats

Rats emit 50-kHz ultrasonic vocalizations (USVs), which reflect positive affective states. Rhythmic stroking increases 50-kHz USVs via the mesolimbic dopaminergic system. However, little is known about the effect of tactile reward on rat brain activity. This study aimed to investigate the brain activity associated with positive emotions induced by tactile stimulation using a frontoparietal electroencephalogram (EEG) as well as through the analysis of 50-kHz USVs and behavioral activity in awake rats. During rhythmic stroking, the power of the middle theta band and harmonics calls significantly increased compared with baseline. After rhythmic stroking, fast theta oscillations significantly increased but slow theta significantly decreased, with abundant frequency-modulated (FM) calls. Light touch stimulation increased the fast theta power but decreased FM calls. However, there was no significant difference in behavior after stimulation with rhythmic stroking or light touch. These results suggest that the characteristic brain theta oscillations and 50-kHz USV profiles induced by tactile reward can detect positive affective states in rats.

The endogenous cannabinoid system modulates male sexual behavior expression.

The endocannabinoid system (ECS) plays a key neuromodulatory role in the brain. Main features of endocannabinoids (eCBs) are that they are produced on demand, in response to enhanced neuronal activity, act as retrograde messengers, and participate in the induction of brain plasticity processes. Sexual activity is a motivated behavior and therefore, the mesolimbic dopaminergic system (MSL) plays a central role in the control of its appetitive component (drive to engage in copulation). In turn, copulation activates mesolimbic dopamine neurons and repeated copulation produces the continuous activation of the MSL system. Sustained sexual activity leads to the achievement of sexual satiety, which main outcome is the transient transformation of sexually active male rats into sexually inhibited animals. Thus, 24 h after copulation to satiety, the sexually satiated males exhibit a decreased sexual motivation and do not respond to the presence of a sexually receptive female with sexual activity. Interestingly, blockade of cannabinoid receptor 1 (CB1R) during the copulation to satiety process, interferes with both the appearance of the long-lasting sexual inhibition and the decrease in sexual motivation in the sexually satiated males. This effect is reproduced when blocking CB1R at the ventral tegmental area evidencing the involvement of MSL eCBs in the induction of this sexual inhibitory state. Here we review the available evidence regarding the effects of cannabinoids, including exogenously administered eCBs, on male rodent sexual behavior of both sexually competent animals and rat sub populations spontaneously showing copulatory deficits, considered useful to model some human male sexual dysfunctions. We also include the effects of cannabis preparations on human male sexual activity. Finally, we review the role played by the ECS in the control of male sexual behavior expression with the aid of the sexual satiety phenomenon. Sexual satiety appears as a suitable model for the study of the relationship between eCB signaling, MSL synaptic plasticity and the modulation of male sexual motivation under physiological conditions that might be useful for the understanding of MSL functioning, eCB-mediated plasticity and their relationship with motivational processes.

Opioid withdrawal: role in addiction and neural mechanisms.

Withdrawal from opioids involves a negative affective state that promotes maintenance of drug-seeking behavior and relapse. As such, understanding the neurobiological mechanisms underlying withdrawal from opioid drugs is critical as scientists and clinicians seek to develop new treatments and therapies. In this review, we focus on the neural systems known to mediate the affective and somatic signs and symptoms of opioid withdrawal, including the mesolimbic dopaminergic system, basolateral amygdala, extended amygdala, and brain and hormonal stress systems. Evidence from preclinical studies suggests that these systems are altered following opioid exposure and that these changes mediate behavioral signs of negative affect such as aversion and anxiety during withdrawal. Adaptations in these systems also parallel the behavioral and psychological features of opioid use disorder (OUD), highlighting the important role of withdrawal in the development of addictive behavior. Implications for relapse and treatment are discussed as well as promising avenues for future research, with the hope of promoting continued progress toward characterizing neural contributors to opioid withdrawal and compulsive opioid use.

Sex differences in dementia with Lewy bodies: an imaging study of neurotransmission pathways

PurposeDementia with Lewy bodies (DLB) is characterized by a wide clinical and biological heterogeneity, with sex differences reported in both clinical and pathologically confirmed DLB cohorts. No research evidence is available on sex differences regarding molecular neurotransmission. This study aimed to assess whether sex can influence neurotransmitter systems in patients with probable DLB (pDLB).MethodsWe included 123 pDLB patients (male/female: 77/46) and 78 control subjects (male/female: 34/44) for comparison, who underwent 123I-FP-CIT SPECT imaging. We assessed sex differences in the dopaminergic activity of the nigrostriatal and mesolimbic systems using regional-based and voxel-wise analyses of 123I-FP-CIT binding. We tested whether sex-specific binding alterations would also pertain to the serotoninergic and noradrenergic systems by applying spatial correlation analyses. We applied molecular connectivity analyses to assess potential sex differences in the dopaminergic pathways.ResultsWe found comparable 123I-FP-CIT binding decreases in the striatum for pDLB males and females compared to controls. However, pDLB females showed lower binding in the extrastriatal projections of the nigrostriatal and mesolimbic dopaminergic systems compared to pDLB males. According to the spatial correlation analysis, sex-specific molecular alterations were also associated with serotonergic and noradrenergic systems. Nigrostriatal and mesolimbic systems’ connectivity was impaired in both groups, with males showing local alterations and females presenting long-distance disconnections between subcortical and cortical regions.ConclusionsSex-specific differences in 123I-FP-CIT binding were found in our cohort, namely, a trend for lower 123I-FP-CIT binding in females, significant in the presence of a pDLB diagnosis. pDLB females showed also different patterns of connectivity compared to males, mostly involving extrastriatal regions. The results suggest the presence of a sex-related regional vulnerability to alpha-synuclein pathology, possibly complicated also by the higher prevalence of Alzheimer’s disease co-pathology in females, as previously reported in pDLB populations.

Recapitulating phenotypes of alcohol dependence via overexpression of Oprk1 in the ventral tegmental area of non-dependent TH::Cre rats

The dynorphin (DYN)/kappa-opioid receptor (KOR) system is involved in dysphoria and negative emotional states. Dysregulation of KOR function promotes maladaptive behavioral regulation during withdrawal associated with alcohol dependence. Mesolimbic dopaminergic (DA) projections from the ventral tegmental area (VTA) innervate the extended amygdala circuitry and presynaptic KORs attenuate DA in these regions leading to an excessive alcohol consumption and negative affective-like behavior, whereas mesocortical KOR-regulated DA projections have been implicated in executive function and decision-making. Thus, the neuroadaptations occurring in DYN/KOR systems are important aspects to consider for the development of personalized therapeutic solutions. Herein, we study the contribution of the VTA DA neuron Oprk1 (KOR gene) in excessive alcohol consumption, negative emotional state, and executive function. To do so, Oprk1 mRNA expression and KOR function were characterized to confirm alcohol dependence-induced dysregulation in the VTA. Then, a transgenic Cre-Lox rat model (male and female TH::Cre rats) was used to allow for conditional and inducible overexpression of Oprk1 in VTA DA neurons. The effect of this overexpression was evaluated on operant alcohol self-administration, negative emotional states, and executive function. We found that VTA Oprk1 overexpression recapitulates some phenotypes of alcohol dependence including escalated alcohol self-administration and depressive-like behavior. However, working memory performance was not impacted following VTA Oprk1 overexpression in TH::Cre rats. This supports the hypothesis that dysregulated KOR signaling within the mesolimbic DA system is an important contributor to symptoms of alcohol dependence and shows that understanding Oprk1-mediated contributions to alcohol use disorder (AUD) should be an important future goal.

Sexual satiety modifies methamphetamine-induced locomotor and rewarding effects and dopamine-related protein levels in the striatum of male rats.

Drug and natural rewarding stimuli activate the mesolimbic dopaminergic system. Both methamphetamine (Meth) and copulation to satiety importantly increase dopamine (DA) release in the nucleus accumbens (NAc), but with differences in magnitude. This paper analyzes the interaction between Meth administration and the intense sexual activity associated with sexual satiety. To evaluate possible changes in Meth-induced behavioral effects and striatal DA-related protein expression due to sexual satiety. Meth-induced locomotor activity and conditioned place preference (CPP) were tested in sexually experienced male rats that copulated to satiety (S-S) or ejaculated once (1E) the day before or displayed no sexual activity (control group; C). DA receptors and DA transporter expression were determined by western blot in the striatum of animals of all sexual conditions treated with specific Meth doses. Meth's locomotor and rewarding effects were exacerbated in S-S animals, while in 1E rats, only locomotor effects were enhanced. Sexual activity, by itself, modified DA-related protein expression in the NAc core and in the caudate-putamen (CPu), while Meth treatment alone changed their expression only in the NAc shell. Meth-induced changes in the NAc shell turned in the opposite direction when animals had sexual activity, and additional changes appeared in the NAc core and CPu of S-S rats. Sexual satiety sensitizes rats to Meth's behavioral effects and the Meth-induced striatal DA-related protein adaptations are modified by sexual activity, evidencing cross-sensitization between both stimuli.

A Thirst for Knowledge: Grounding Curiosity, Creativity, and Aesthetics in Memory and Reward Neural Systems

ABSTRACT Curiosity, creativity, and aesthetics are typically studied separately. The extent to which they share psychological and neural mechanisms is not well understood, despite all being linked to broader personality characteristics like Openness to Experience and are driven by a desire for information and knowledge. Here, we review evidence and advance the hypothesis that creative and aesthetic experiences depend on curiosity as a driver of information-seeking and exploratory behavior because they are exemplars of situations that highlight gaps in knowledge or require problem finding and solving. At the psychological level, we link curiosity, creativity, and aesthetics to Openness to Experience and to ones’ semantic memory. We demonstrate how Openness is a critical personality trait in enhancing curious behaviors, as well as creative and aesthetic acts. Furthermore, we highlight the role of semantic memory in such information-seeking behavior, leading to knowledge acquisition. At the neural level, we examine the neurobiological underpinnings of these constructs in relation to the mesolimbic dopaminergic reward system, as related to information-seeking. Finally, we link creativity and aesthetic experience and discuss how stages of art viewing and making relate to curiosity. Thus, we argue that information-seeking, the key behavior attributed to curiosity, motivates both creative and aesthetic activities.

The Role of Intra-Amygdaloid Neurotensin and Dopamine Interaction in Spatial Learning and Memory.

Neurotransmitter and neuromodulator neurotensin (NT) has been proved to facilitate spatial and passive avoidance learning after microinjected into the rat central nucleus of amygdala (CeA). These previous studies of our laboratory also revealed that neurotensin-1 receptor (NTS1) is involved in the mentioned actions of NT. Extensive literature confirms the interaction between neurotensinergic and dopaminergic systems, and our research group also suppose that the mesolimbic dopaminergic system (MLDS) is involved in the spatial learning and memory-facilitating effect of NT in the CeA. In the present work, NT and dopamine (DA) interaction has been examined in the Morris water maze and passive avoidance tests. Rats received 100 ng NT, 5 µg dopamine D2 receptor antagonist sulpiride in itself, sulpiride as a pretreatment before NT or vehicle solution into the CeA. NT microinjection significantly decreased target-finding latency in the Morris water maze test and significantly increased entrance latency in the passive avoidance test, as was expected based on our previous findings. The DA D2 receptor antagonist pretreatment was able to inhibit both effects of NT. The results confirm the facilitatory effect of NT on spatial learning and memory and let us conclude that these actions can be exerted via the DA D2 receptors.

Protein kinases in natural versus drug reward

Natural and drug rewards act on the same neural pathway, the mesolimbic dopaminergic system. In brain regions such as the nucleus accumbens and ventral tegmental area, drugs of abuse-induced stimulation of signaling pathways can lead to synaptic reshaping within this system. This is believed to be underlying the maladaptive alterations in behaviors associated with addiction.In this review, we discuss animal studies disclosing the implication of several protein kinases, namely protein kinase A (PKA), extracellular signal regulated kinase (ERK) mitogen-activated protein kinases (MAPK), p38 MAPK, and calcium/calmodulin-dependent kinase II (CaMKII), in reward-related brain regions in drug and natural reward. Furthermore, we refer to studies that helped pave the way toward a better understanding of the neurobiology underlying non-drug and drug reward through genetic deletion or brain region-specific pharmacological inhibition of these kinases.Whereas the role of kinases in drug reward has been extensively studied, their implication in natural reward, such as positive social interaction, is less investigated. Discovering molecular candidates, recruited specifically by drug versus natural rewards, can promote the identification of novel targets for the pharmacological treatment of addiction with less off-target effects and being effective when used combined with behavioral-based therapies.

Maternal Methyl-Enriched Diet Increases Dopaminergic Tone of the Mesolimbic Brain System in Adult Offspring of WAG/Rij Rats.

The aim of this study is to find out whether maternal methyl-enriched diet affects the content of monoamines and their metabolites in brain structures of adult WAG/Rij offspring. It has been shown for the first time that maternal methyl-enriched diet (choline, betaine, folic acid, vitamin B12, L-methionine, zink) during the perinatal period increases dopaminergic tone of the mesolimbic brain system in adult offspring of WAG/Rij rats, which is accompanied by the suppression of the symptoms of genetic absence epilepsy and comorbid depression. Results suggest that maternal methyl-enriched diet during the perinatal period may be served as a new therapeutic strategy to prevent the development of a hypofunction of the mesolimbic dopaminergic brain system and associated genetic absence epilepsy and comorbid depression in offspring.