There is a gap in existing knowledge of stress-triggered neurochemical and behavioral adaptations in females. This study was designed to explore the short-term consequences of a single social defeat (SD) on accumbal dopamine (DA) dynamics and related behaviors in female Wistar rats. During the SD procedure, rats demonstrated different stress-handling strategies, which were defined as active and passive coping.
View Article and Find Full Text PDFBackground: The dopamine transporter (DAT) is the main regulator of dopamine concentration in the extrasynaptic space. The pharmacological inhibition of the DAT results in a wide spectrum of behavioral manifestations, which have been identified so far in a limited number of species, mostly in rodents.
Aim: Here, we used another well-recognized model organism, the zebrafish (), to explore the behavioral effects of GBR 12909, a highly-affine selective DAT blocker.
The present study aimed to explore the consequences of a single exposure to a social defeat on dopamine release in the rat nucleus accumbens measured with a fast-scan cyclic voltammetry. We found that 24 h after a social defeat, accumbal dopamine responses, evoked by a high frequency electrical stimulation of the ventral tegmental area, were more profound in socially defeated rats in comparison with non-defeated control animals. The enhanced dopamine release was associated with the prolonged immobility time in the forced swim test.
View Article and Find Full Text PDFThe Trace Amine-Associated Receptor 1 (TAAR1) is one of the six functional receptors belonging to the family of monoamine-related G protein-coupled receptors (TAAR1-TAAR9) found in humans. However, the exact biological mechanisms of TAAR1 central and peripheral action remain to be fully understood. TAAR1 is widely expressed in the prefrontal cortex and several limbic regions, interplaying with the dopamine system to modulate the reward circuitry.
View Article and Find Full Text PDFProgress in the development of technologies for the real-time monitoring of neurotransmitter dynamics has provided researchers with effective tools for the exploration of etiology and molecular mechanisms of neuropsychiatric disorders. One of these powerful tools is fast-scan cyclic voltammetry (FSCV), a technique which has progressively been used in animal models of diverse pathological conditions associated with alterations in dopamine transmission. Indeed, for several decades FSCV studies have provided substantial insights into our understanding of the role of abnormal dopaminergic transmission in pathogenetic mechanisms of drug and alcohol addiction, Parkinson's disease, schizophrenia, etc.
View Article and Find Full Text PDFTrace amines are a group of biogenic amines that are structurally and functionally close to classical monoamine neurotransmitters. Trace amine-associated receptors (TAARs) are emerging as promising targets for treating neuropsychiatric disorders. It has been documented that all TAARs, apart from TAAR1, function as olfactory receptors involved in sensing innate odors encoded by volatile amines.
View Article and Find Full Text PDFUsing a variety of animal models that simulate key features of the alcohol use disorder (AUD), remarkable progress has been made in identifying neurochemical targets that may contribute to the development of alcohol addiction. In this search, the dopamine (DA) and norepinephrine (NE) systems have been long thought to play a leading role in comparison with other brain systems. However, just recent development and application of optogenetic approaches into the alcohol research field provided opportunity to identify neuronal circuits and specific patterns of neurotransmission that govern the key components of ethanol-addictive behaviors.
View Article and Find Full Text PDFThe current rodent study applied fast-scan cyclic voltammetry (FSCV), paired with a pharmacological approach, to measure the release of the catecholamines (CA) dopamine (DA) and norepinephrine (NE) in the basolateral amygdala (BLA) following locus coeruleus (LC) stimulation. The primary goal was to determine if exposure to either social (social defeat) or non-social (forced swim) stress altered LC-evoked catecholamine release dynamics in the BLA. We used idazoxan (α2 adrenergic receptor antagonist) and raclopride (D dopamine receptor antagonist) to confirm the presence of NE and DA, respectively, in the measured CA signal.
View Article and Find Full Text PDFThe relationship between stress and alcohol-drinking behaviors has been intensively explored; however, neuronal substrates and neurotransmitter dynamics responsible for a causal link between these conditions are still unclear. Here, we optogenetically manipulated locus coeruleus (LC) norepinephrine (NE) activity by applying distinct stimulation protocols in order to explore how phasic and tonic NE release dynamics control alcohol-drinking behaviors. Our results clearly demonstrate contrasting behavioral consequences of LC-NE circuitry activation during low and high frequency stimulation.
View Article and Find Full Text PDFDespite many years of work on dopaminergic mechanisms of alcohol addiction, much of the evidence remains mostly correlative in nature. Fortunately, recent technological advances have provided the opportunity to explore the causal role of alterations in neurotransmission within circuits involved in addictive behaviors. Here, we address this critical gap in our knowledge by integrating an optogenetic approach and an operant alcohol self-administration paradigm to assess directly how accumbal dopamine (DA) release dynamics influences the appetitive (seeking) component of alcohol-drinking behavior.
View Article and Find Full Text PDFUsing fast-scan cyclic voltammetry paired with pharmacology, the authors show that infralimbic catecholamine release following locus coeruleus stimulation is noradrenergic, but not dopaminergic, and not affected by acute ethanol. With previous work, these data suggest differential effects of ethanol on prefrontal norepinephrine and dopamine, a region important in addiction-related pathways.
View Article and Find Full Text PDFActivity in the mesolimbic dopamine (DA) pathway is known to have a role in reward processing and related behaviors. The mesolimbic DA response to reward has been well-examined, while the response to aversive or negative stimuli has been studied to a lesser extent and produced inconclusive results. However, a brief increase in the DA concentration in terminals during nociceptive activation has become an established but not well-characterized phenomenon.
View Article and Find Full Text PDFDopamine (DA) controls many vital physiological functions and is critically involved in several neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder. The major function of the plasma membrane dopamine transporter (DAT) is the rapid uptake of released DA into presynaptic nerve terminals leading to control of both the extracellular levels of DA and the intracellular stores of DA. Here, we present a newly developed strain of rats in which the gene encoding DAT knockout Rats (DAT-KO) has been disrupted by using zinc finger nuclease technology.
View Article and Find Full Text PDFThe current study aimed to explore how presynaptic dopamine (DA) function is altered following brief stress episodes and chronic ethanol self-administration and whether these neuroadaptations modify the acute effects of ethanol on DA dynamics. We used fast-scan cyclic voltammetry to evaluate changes in DA release and uptake parameters in rat nucleus accumbens brain slices by analyzing DA transients evoked through single pulse electrical stimulation. Adult male rats were divided into four groups: ethanol-naïve or ethanol drinking (six week intermittent two-bottle choice) and stressed (mild social defeat) or nonstressed.
View Article and Find Full Text PDFRecent studies have used conditional knockout mice to selectively delete the D2 autoreceptor; however, these approaches result in global deletion of D2 autoreceptors early in development. The present study takes a different approach using RNA interference (RNAi) to knockdown the expression of the D2 receptors (D2R) in the substantia nigra (SN), including dopaminergic neurons, which project primarily to the dorsal striatum (dStr) in adult rats. This approach restricts the knockdown primarily to nigrostriatal pathways, leaving mesolimbic D2 autoreceptors intact.
View Article and Find Full Text PDFNeural networks that control reproduction must integrate social and hormonal signals, tune motivation, and coordinate social interactions. However, the neural circuit mechanisms for these processes remain unresolved. The medial preoptic area (mPOA), an essential node for social behaviors, comprises molecularly diverse neurons with widespread projections.
View Article and Find Full Text PDFRecent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 2016
Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson's disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats.
View Article and Find Full Text PDFThe dopamine transporter (DAT) plays an important homeostatic role in the control of both the extracellular and intraneuronal concentrations of dopamine, thereby providing effective control over activity of dopaminergic transmission. Since brain dopamine is known to be involved in numerous neuropsychiatric disorders, investigations using mice with genetically altered DAT function and thus intensity of dopamine-mediated signaling have provided numerous insights into the pathology of these disorders and novel pathological mechanisms that could be targeted to provide new therapeutic approaches for these disorders. In this brief overview, we discuss recent investigations involving animals with genetically altered DAT function, particularly focusing on translational studies providing new insights into pathology and pharmacology of dopamine-related disorders.
View Article and Find Full Text PDFBackground: Adenosine serves many functions within the CNS, including inhibitory and excitatory control of neurotransmission. The understanding of adenosine dynamics in the brain is of fundamental importance. The goal of the present study was to explore subsecond adenosine fluctuations in the rat brain in vivo.
View Article and Find Full Text PDFTechniques to genetically manipulate the activity of defined neuronal subpopulations have been useful in elucidating function, however applicability to translational research beyond transgenic mice is limited. Subtype targeted transgene expression can be achieved using specific promoters, but often currently available promoters are either too large to package into many vectors, in particular adeno-associated virus (AAV), or do not drive expression at levels sufficient to alter behavior. To permit neuron subtype specific gene expression in wildtype animals, we developed a combinatorial AAV targeting system that drives, in combination, subtype specific Cre-recombinase expression with a strong but non-specific Cre-conditional transgene.
View Article and Find Full Text PDFCentral dopamine and norepinephrine regulate behavioral and physiological responses during rewarding and aversive stimuli. Here, we investigated and compared norepinephrine and dopamine transmission in 2 limbic structures, the ventral bed nucleus of the stria terminalis and the nucleus accumbens shell of anesthetized rats, respectively, in response to acute tail pinch, a noxious stimulus. Norepinephrine release in the ventral bed nucleus of the stria terminalis responded monophasically, increasing at the time of the tail pinch and remaining elevated for a period after its cessation.
View Article and Find Full Text PDFThere is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive.
View Article and Find Full Text PDFIn this study, the first in-depth analysis of optically induced dopamine release using fast-scan cyclic voltammetry on striatal slices from rat brain was performed. An adeno-associated virus that expresses Channelrhodopsin-2 was injected in the substantia nigra. Tissue was collected and sectioned into 400μm-thick coronal slices 4 weeks later.
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