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ventral tegmental area (VTA)

Michael P Saddoris
Repeated self-administration of cocaine is associated with impairments in motivated behaviors as well as alterations in both dopamine (DA) release and neural signaling within the nucleus accumbens (NAc). These impairments are present even after several weeks of abstinence from drug taking, suggesting that the self-administration experience induces long-lasting neuroplastic alterations in the mesolimbic DA circuit. To understand these changes at the terminal level, rats were allowed to self-administer either cocaine intravenously (∼1 mg/kg per infusion) or water to a receptacle (control) in 2-h sessions over 14 days, followed by 30 days of enforced abstinence...
September 2016: ENeuro
Linde Boekhoudt, Elisa S Voets, Jacques P Flores-Dourojeanni, Mieneke Cm Luijendijk, Louk Jmj Vanderschuren, Roger Ah Adan
Attentional impairments and exaggerated impulsivity are key features of psychiatric disorders, such as attention-deficit/hyperactivity disorder, schizophrenia, and addiction. These deficits in attentional performance and impulsive behaviours have been associated with aberrant dopamine (DA) signalling, but it remains unknown whether these deficits result from enhanced DA neuronal activity in the midbrain. Here, we took a novel approach by testing the impact of chemogenetically activating DA neurons in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) on attention and impulsivity in the five-choice serial reaction time task (5-CSRTT) in rats...
October 17, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Jianli Wang, Chaobao Liu, Yongping Ma
Parents-offspring bonding is critical for development of offspring in mammals. While it is known that pups stimuli provide rewarding effects on their parents, few studies have assessed whether parental stimuli serve as a reinforcing agent to their pups, and what the neural mechanisms underlying this reward process may be. In addition to maternal care, male ICR mice display pairmate-dependent parental behavior. Using the conditioned place preference (CPP) paradigm, we examined the effects of maternal and paternal conditioning on the postnatal day 17-21 female ICR mice pups, and compared the central expression of oxytocin (OT)- and tyrosine hydroxylase (TH)- immunoreactive (IR) neurons...
October 13, 2016: Behavioural Brain Research
Stephan Steidl, Huiling Wang, Marco Ordonez, Shiliang Zhang, Marisela Morales
Converging evidence shows that ventral tegmental area (VTA) dopamine neurons receive laterodorsal tegmental nucleus (LDTg) cholinergic and glutamatergic inputs. To test the behavioral consequences of selectively driving the two sources of excitatory LDTg input to the VTA, channelrhodopsin-2 (ChR2) was expressed in LDTg cholinergic neurons of ChAT::Cre mice (ChAT-ChR2 mice) or in LDTg glutamatergic neurons of VGluT2::Cre mice (VGluT2-ChR2 mice). Mice were tested in a 3-chamber place preference apparatus where entry into a light-paired chamber resulted in VTA light stimulation of LDTg-cholinergic or LDTg-glutamatergic axons for the duration of a chamber stay...
October 14, 2016: European Journal of Neuroscience
Sudarat Nimitvilai, Chang You, Devinder S Arora, Maureen A McElvain, Bertha J Vandegrift, Mark S Brodie, John J Woodward
Drugs of abuse increase the activity of dopaminergic neurons of the ventral tegmental area (VTA), and output from the VTA is critical for both natural and drug-induced reward and reinforcement. Ethanol and the abused inhalant toluene both enhance VTA neuronal firing, but the mechanisms of this effect is not fully known. In this study, we used extracellular recordings to compare the actions of toluene and ethanol on DA VTA neurons. Both ethanol and toluene increased the firing rate of DA neurons, although toluene was ~100 times more potent than ethanol...
2016: Frontiers in Neuroscience
Linde Boekhoudt, Azar Omrani, Mieneke C M Luijendijk, Inge G Wolterink-Donselaar, Ellen C Wijbrans, Geoffrey van der Plasse, Roger A H Adan
Hyperactivity is a core symptom in various psychiatric disorders, including attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorders, and anorexia nervosa. Although hyperactivity has been linked to dopaminergic signalling, the causal relationship between midbrain dopamine neuronal activity and locomotor hyperactivity remains unknown. In this study, we test whether increased dopamine neuronal activity is sufficient to induce locomotor hyperactivity. To do so, we used designer receptors exclusively activated by designer drugs (DREADD) to chemogenetically enhance neuronal activity in two main midbrain dopamine neuron populations, i...
October 3, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Wendy Xin, Nicholas Edwards, Antonello Bonci
Dopamine neurons in the ventral tegmental area are involved in a variety of physiological and pathological conditions, ranging from motivated behaviors to substance use disorders. While many studies have shown that these neurons can express plasticity at excitatory and inhibitory synapses, little is known about how inhibitory inputs and glial activity shape the output of DA neurons and therefore, merit greater discussion. In this review, we will attempt to fill in a bit more of the puzzle, with a focus on inhibitory transmission and astrocyte function...
October 6, 2016: European Journal of Neuroscience
Cristian Arredondo, Marcela González, María Estela Andrés, Katia Gysling
Dopamine neurons are overstimulated by drugs of abuse and suffer molecular alterations that lead to addiction behavior. Nurr1 is a transcription factor crucial for dopamine neurons survival and dopamine production, activating the transcription of key genes like tyrosine hydroxylase (TH). Interestingly, nuclear factor-kappa B (NF-κB) has emerged as a new Nurr1 partner in response to inflammatory stimulus. In this study we evaluated the effects of single and repeated amphetamine administration in the expression of Nurr1 and the NF-κB p65 subunit in the rat ventral tegmental area (VTA)...
September 26, 2016: Brain Research
Amita R Somalwar, Gajanan P Shelkar, Nishikant K Subhedar, Dadasaheb M Kokare
Rats with electrode implanted in the lateral hypothalamus (LH)-medial forebrain bundle (MFB) area actively engage in intracranial self-stimulation (ICSS). However, the neuronal substrate that translates the electrical pulses into the neural signals, and integrates the information with mesolimbic reward system, has remained elusive. We test the hypothesis that the cocaine- and amphetamine-regulated transcript (CART) neurons in the LH-MFB area may support this function. The ICSS activity via an electrode in LH-MFB area was facilitated by CART (55-102) peptide stereotaxically injected in the lateral ventricle or posterior ventral tegmental area (pVTA), but attenuated by CART antibody...
September 27, 2016: Behavioural Brain Research
M Carmen Blanco-Gandía, Lídia Cantacorps, Auxiliadora Aracil-Fernández, Sandra Montagud-Romero, María A Aguilar, Jorge Manzanares, Olga Valverde, José Miñarro, Marta Rodríguez-Arias
Binge eating is a specific form of overeating characterized by intermittent excessive eating. In addition to altering the neurobiological reward system, several studies have highlighted that consumption of palatable food increases vulnerability to drug use. The aim of the present study was to evaluate the effects of a high-fat diet consumed in a binge pattern during adolescence on the reinforcing effects of cocaine. After 40 days of binge-eating for 2 h, three days a week (PND 29-69), the reinforcing effects of cocaine on conditioning place preference and intravenous self-administration paradigm were evaluated in adolescent male mice...
September 22, 2016: Neuropharmacology
Lauren N Beloate, Azar Omrani, Roger A Adan, Ian C Webb, Lique M Coolen
UNLABELLED: Experience with sexual behavior causes cross-sensitization of amphetamine reward, an effect dependent on a period of sexual reward abstinence. We previously showed that ΔFosB in the nucleus accumbens (NAc) is a key mediator of this cross-sensitization, potentially via dopamine receptor activation. However, the role of mesolimbic dopamine for sexual behavior or cross-sensitization between natural and drug reward is unknown. This was tested using inhibitory designer receptors exclusively activated by designer drugs in ventral tegmental area (VTA) dopamine cells...
September 21, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Niels R Ntamati, Christian Lüscher
Both dopamine and nondopamine neurons from the ventral tegmental area (VTA) project to a variety of brain regions. Here we examine nondopaminergic neurons in the mouse VTA that send long-range projections to the hippocampus. Using a combination of retrograde tracers, optogenetic tools, and electrophysiological recordings, we show that VTA GABAergic axons make synaptic contacts in the granule cell layer of the dentate gyrus, where we can elicit small postsynaptic currents. Surprisingly, the currents displayed a partial sensitivity to both bicuculline and NBQX, suggesting that these mesohippocampal neurons corelease both GABA and glutamate...
July 2016: ENeuro
Naofumi Taoka, Ryota Kamiizawa, Shintaro Wada, Masabumi Minami, Katsuyuki Kaneda
The laterodorsal tegmental nucleus (LDT), which sends cholinergic efferent connections to dopaminergic (DA) neurons in the ventral tegmental area (VTA), plays a critical role in the development of addictive behavior and the reinstatement of cocaine-seeking behavior. Although repeated cocaine exposure elicits plastic changes in excitatory synaptic transmission and intrinsic membrane excitability in LDT cholinergic neurons, it remains unclear whether inhibitory synaptic transmission is modulated by cocaine exposure...
September 20, 2016: European Journal of Neuroscience
Hamdy Shaban, Rory O'Connor, Saak V Ovsepian, Timothy G Dinan, John F Cryan, Harriët Schellekens
Hypothalamic neural circuits are recognised as primary sites of the neuromodulator effect of homeostatic food intake, whereas changes in ventral tegmental area (VTA), hippocampus and amygdala have been implicated in the hedonic, cognitive and emotional aspects of eating. Here, we discuss synaptic transmission and plasticity within brain circuits governing appetite and food intake behaviour, focusing on the metabolic hormones ghrelin and leptin. We discuss functional changes within these circuitries and critically assess the applicability of electrophysiological measurements using in vitro multielectrode array (MEA) systems to identify novel appetite modulators...
September 12, 2016: Drug Discovery Today
Zhimin Song, Johnathan M Borland, Tony E Larkin, Maureen O'Malley, H Elliott Albers
Social reward plays a fundamental role in shaping human and animal behavior. The rewarding nature of many forms of social behavior including sexual behavior, parental behavior, and social play has been revealed using well-established procedures such as the conditioned place preference test. Many motivated social behaviors are regulated by the nonapeptides oxytocin (OT) and arginine vasopressin (AVP) through their actions in multiple brain structures. Interestingly, there are few data on whether OT or AVP might contribute to the rewarding properties of social interaction by their actions within brain structures that play a key role in reward mechanisms such as the ventral tegmental area (VTA)...
September 9, 2016: Psychoneuroendocrinology
Joanna Peris, Kaley MacFadyen, Justin A Smith, Annette D de Kloet, Lei Wang, Eric G Krause
The mesolimbic dopamine (DA) circuitry determines which behaviors are positively reinforcing and therefore should be encoded in the memory to become a part of the behavioral repertoire. Natural reinforcers, like food and sex, activate this pathway, thereby increasing the likelihood of further consummatory, social, and sexual behaviors. Oxytocin (OT) has been implicated in mediating natural reward and OT-synthesizing neurons project to the ventral tegmental area (VTA) and nucleus accumbens (NAc); however, direct neuroanatomical evidence of OT regulation of DA neurons within the VTA is sparse...
September 12, 2016: Journal of Comparative Neurology
Devin P Merullo, Caroline S Angyal, Sharon A Stevenson, Lauren V Riters
Some animals, including songbirds, vocalize at high rates when alone or in large groups. In songbirds, vocal behavior in these contexts is important for song learning and group cohesion. It is not obviously targeted at any particular individual and is described as 'undirected'. Studies suggest a role for dopamine (DA) in undirected song. The neuropeptide neurotensin (NT) can enhance dopaminergic signaling upon binding to the NT receptor 1 (NTR1) and is found in regions where DA can influence song, including the ventral tegmental area (VTA), septum, and the song control nucleus Area X...
September 10, 2016: Brain, Behavior and Evolution
M C Arenas, A Mateos-García, C Manzanedo, M Rodríguez-Arias, M A Aguilar, F Navarrete, M S García Gutiérrez, J Manzanares, J Miñarro
RATIONALE: Topiramate is an anticonvulsant drug which has been evaluated as a therapeutic option for the treatment of cocaine addiction during the last decade. OBJECTIVES: The purpose of this study was to evaluate the effects of topiramate on the reinforcing actions of cocaine. To this aim, the topiramate-mediated regulation of acquisition and extinction phases of the cocaine conditioned place preference (CPP) was assessed in young-adult mice using three experimental designs...
September 5, 2016: Psychopharmacology
Ada Eban-Rothschild, Gideon Rothschild, William J Giardino, Jeff R Jones, Luis de Lecea
Dopaminergic ventral tegmental area (VTA) neurons are critically involved in a variety of behaviors that rely on heightened arousal, but whether they directly and causally control the generation and maintenance of wakefulness is unknown. We recorded calcium activity using fiber photometry in freely behaving mice and found arousal-state-dependent alterations in VTA dopaminergic neurons. We used chemogenetic and optogenetic manipulations together with polysomnographic recordings to demonstrate that VTA dopaminergic neurons are necessary for arousal and that their inhibition suppresses wakefulness, even in the face of ethologically relevant salient stimuli...
October 2016: Nature Neuroscience
Limin Xu, Qingxiao Hong, Xiaoying Chen, Xuting Xu, Huifen Liu, Wenhua Zhou, Shiwei Duan
Diacetylmorphine hydrochloride (heroin) addiction is a chronic relapsing brain disorder that is a heavy public health burden worldwide. Brm/SWI2-related gene-1 (BRG1) is a tumor suppressor gene that can influence embryogenesis and the development of the cerebellum. The current study aimed to investigate the effect of histone H4 lysine 5 (H4K5) modifications on the BRG1 gene in brain tissue of the ventral tegmental area (VTA) of heroin-addicted rats. A total of 21 male Sprague Dawley rats were raised in a standard manner and underwent heroin self-administration training...
September 2016: Experimental and Therapeutic Medicine
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