Phasic dopamine release in two different rat models of attention-deficit/hyperactivity disorder: Spontaneously hypertensive rats (SHR) versus Lphn3 knockout rats.

We examined DA activity in the medial prefrontal cortex (mPFC) and nucleus accumbens core (NAcc) in two Different Rat Models of Attention-Deficit/Hyperactivity Disorder: Spontaneously Hypertensive Rats (SHR) Versus Lphn3 Knockout Rats. We examined baseline stimulation-evoked phasic DA release, half-life, and DA autoreceptor (DAR) functioning in the mPFC and NAcc, as well as the response to nomifensine (10 mg/kg, IP), a DA transporter (DAT) blocker, on these measures in the NAcc. Both rat models were hypodopaminergic, with notable regional and mechanistic differences.

Memphis NeuroSTART Program: Promoting Student Success and Increasing the Diversity of Applicants to Neuroscience Graduate Programs.

With grant support from the Research Experience for Undergraduates (REU) program funded by the National Science Foundation (NSF) and the Awards to Stimulate and Support Undergraduate Research Experiences (ASSURE) program funded by the Department of Defense (DoD) Air Force Office of Scientific Research (AFOSR), we established a program intended to increase the number of underrepresented racial and ethnic minority (URM) and first-generation undergraduate students successfully applying to neuroscience and other STEM-related graduate programs. The Neuroscience Techniques and Research Training (NeuroSTART) Program aimed to increase the number of undergraduate students from the Memphis area involved in behavioral neuroscience research. In this two-semester program, students completed an empirical research project in a neuroscience lab, received individual mentoring from neuroscience faculty, became part of a STEM network, presented at research conferences, and attended specialized professional development seminars.

Indirect and direct cannabinoid agonists differentially affect mesolimbic dopamine release and related behaviors.

The cannabinoid system is being researched as a potential pharmaceutical target for a multitude of disorders. The present study examined the effect of indirect and direct cannabinoid agonists on mesolimbic dopamine release and related behaviors in C57BL/6J (B6) mice. The indirect cannabinoid agonist N-arachidonoyl serotonin (AA-5-HT) indirectly agonizes the cannabinoid system by preventing the metabolism of endocannabinoids through fatty acid amide hydrolase inhibition while also inhibiting transient receptor potential vanilloid Type 1 channels.

A Special Issue on the Roles of Dopamine in Neural Circuits, Genetics, and Behavior.

Over the past 80 years, research on dopamine has undergone significant evolution, reshaping our understanding of its roles in the brain and the body [...

Effects of isolation housing stress and mouse strain on intravenous cocaine self-administration, sensory stimulus self-administration, and reward preference.

Sensory stimuli are natural rewards in mice and humans. Consequently, preference for a drug reward relative to a sensory reward may be an endophenotype of addiction vulnerability. In this study, we developed a novel behavioral assay to quantify the preference for intravenous drug self-administration relative to sensory stimulus self-administration.

Age-dependent effects of social isolation on mesolimbic dopamine release.

In humans, social isolation is a known risk factor for disorders such as substance use disorder and depression. In rodents, social isolation is a commonly used environmental manipulation that increases the occurrence of behaviors related to these disorders. Age is thought to influence the effects of social isolation, but this predictive relationship is not well-understood.

An assessment of executive function in two different rat models of attention-deficit hyperactivity disorder: Spontaneously hypertensive versus Lphn3 knockout rats.

Attention-deficit/hyperactivity disorder (ADHD) a common neurodevelopmental disorder of childhood and often comorbid with other externalizing disorders (EDs). There is evidence that externalizing behaviors share a common genetic etiology. Recently, a genome-wide, multigenerational sample linked variants in the Lphn3 gene to ADHD and other externalizing behaviors.

A high fat western diet attenuates phasic dopamine release.

Natural rewards, such as food and social interaction, as well as drugs of abuse elicit increased mesolimbic dopamine release in the nucleus accumbens (NAc). Drugs of abuse, however, increase NAc dopamine release to a greater extent and are known to induce lasting changes on the functioning of the mesolimbic dopamine pathway. Less is known about the long-term effects of diet composition on this reward pathway.

Risky decision-making predicts dopamine release dynamics in nucleus accumbens shell.

The risky decision-making task (RDT) measures risk-taking in a rat model by assessing preference between a small, safe reward and a large reward with increasing risk of punishment (mild foot shock). It is well-established that dopaminergic drugs modulate risk-taking; however, little is known about how differences in baseline phasic dopamine signaling drive individual differences in risk preference. Here, we used in vivo fixed potential amperometry in male Long-Evans rats to test if phasic nucleus accumbens shell (NACs) dopamine dynamics are associated with risk-taking.

Cerebellar Modulation of Mesolimbic Dopamine Transmission Is Functionally Asymmetrical.

Cerebral and cerebellar hemispheres are known to be asymmetrical in structure and function, and previous literature supports that asymmetry extends to the neural dopamine systems. Using in vivo fixed potential amperometry with carbon fiber microelectrodes in anesthetized mice, the current study assessed hemispheric lateralization of stimulation-evoked dopamine in the nucleus accumbens (NAc) and the influence of the cerebellum in regulating this reward-associated pathway. Our results suggest that cerebellar output can modulate mesolimbic dopamine transmission, and this modulation contributes to asymmetrically lateralized dopamine release.

Systemic oxytocin administration alters mesolimbic dopamine release in mice.

Growing research indicates oxytocin may be involved in relieving anxiety and attenuating the rewarding effects of psychostimulants. This study investigated the effects of subchronic oxytocin treatments on mesolimbic dopamine transmission in areas associated with anxiety and addiction, the amygdala and the nucleus accumbens (NAc), respectively. Using in vivo fixed potential amperometry, stimulation-evoked dopamine release was recorded in anesthetized mice pretreated with subchronic oxytocin (four i.

Arachidonoyl serotonin (AA-5-HT) modulates general fear-like behavior and inhibits mesolimbic dopamine release.

Cannabinergic and vanilloidergic signaling are potential mechanisms for the treatment of anxiety symptoms because of the anxiolytic properties of cannabinoid type 1 receptor (CBR) activation and transient potential vanilloid type 1 channel (TRPV) inhibition. Arachidonoyl serotonin (AA-5-HT), a fatty acid amide hydrolase and TRPV inhibitor provides a means of modulating these systems. We examined the effects of AA-5-HT on anxiety- and fear-like behaviors in male low (C57BL/6 J; [B6]) and high (BALB/cJ; [BCJ]) anxiety mice in light/dark box (LDB), open-field (OF), and fear extinction (FE) paradigms.

Comparing phasic dopamine dynamics in the striatum, nucleus accumbens, amygdala, and medial prefrontal cortex.

Midbrain dopaminergic neurons project to and modulate multiple highly interconnected modules of the basal ganglia, limbic system, and frontal cortex. Dopamine regulates behaviors associated with action selection in the striatum, reward in the nucleus accumbens (NAc), emotional processing in the amygdala, and executive functioning in the medial prefrontal cortex (mPFC). The multifunctionality of dopamine likely occurs at the individual synapses, with varied levels of phasic dopamine release acting on different receptor populations.

Genotype-dependent effects of adolescent nicotine exposure on dopamine functional dynamics in the nucleus accumbens shell in male and female mice: a potential mechanism underlying the gateway effect of nicotine.

Rationale: The tendency to use cocaine is determined by genetic and environmental effects across the lifespan. One critical environmental effect is early drug exposure, which is both driven by and interacts with genetic background. The mesoaccumbens dopamine system, which is critically involved in the rewarding properties of drugs of abuse, undergoes significant development during adolescence, and thus may be at particular risk to repeated nicotine exposure during this period, thereby establishing vulnerability for subsequent adult psychostimulant use.

Acetylcholine-dopamine interactions in the pathophysiology and treatment of CNS disorders.

Dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area of the midbrain form the nigrostriatal and mesocorticolimbic dopaminergic pathways that, respectively, project to dorsal and ventral striatum (including prefrontal cortex). These midbrain dopaminergic nuclei and their respective forebrain and cortical target areas are well established as serving a critical role in mediating voluntary motor control, as evidenced in Parkinson's disease, and incentive-motivated behaviors and cognitive functions, as exhibited in drug addiction and schizophrenia, respectively. Although it cannot be disputed that excitatory and inhibitory amino acid-based neurotransmitters, such as glutamate and GABA, play a vital role in modulating activity of midbrain dopaminergic neurons, recent evidence suggests that acetylcholine may be as important in regulating dopaminergic transmission.

Neuronal pathways involved in deep brain stimulation of the subthalamic nucleus for treatment of Parkinson's disease.

In this study, fixed potential amperometry was used to examine several pathways by which Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) or dopamine axons within the dorsal forebrain bundle (DFB) release striatal dopamine, thus potentially providing therapeutic benefits for Parkinson's Disease patients. In urethane anesthetized mice, electrical stimulations (20 monophasic pulses at 50 Hz every 30 sec) were applied to the STN or DFB while infusing the local anesthetic lidocaine (4%) into the substantia nigra compacta (SNc) or pedunculopontine tegmental nucleus (PPT). Findings suggest that DFB stimulation activates ascending SNc dopamine axons, while STN stimulation evokes striatal dopamine release directly via excitatory glutamatergic inputs to SNc dopamine cells and indirectly via excitatory cholinergic/glutamatergic STN-PPT-SNc pathways.

Muscarinic receptor blockade in the ventral tegmental area attenuates cocaine enhancement of laterodorsal tegmentum stimulation-evoked accumbens dopamine efflux in the mouse.

The reinforcing properties of cocaine have been related to increased extracellular concentrations of dopamine in the nucleus accumbens (NAc). M5 muscarinic acetylcholine receptors (mAChRs) on dopamine cells in the ventral tegmental area (VTA) facilitate mesoaccumbens dopamine transmission and are critically involved in mediating natural and drug reinforcement. We investigated the effects of pharmacological blockade of mAChRs in the VTA on cocaine's ability to enhance electrically evoked NAc dopamine efflux.

Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice.

Introduction: Muscarinic M(5) receptors are the only muscarinic receptor subtype expressed by dopamine-containing neurons of the ventral tegmental area. These cells play an important role for the reinforcing properties of psychostimulants and M(5) receptors modulate their activity. Previous studies showed that M(5) receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs.

Evolution of Deep Brain Stimulation: Human Electrometer and Smart Devices Supporting the Next Generation of Therapy.

Deep Brain Stimulation (DBS) provides therapeutic benefit for several neuropathologies including Parkinson's disease (PD), epilepsy, chronic pain, and depression. Despite well established clinical efficacy, the mechanism(s) of DBS remains poorly understood. In this review we begin by summarizing the current understanding of the DBS mechanism.

Midbrain acetylcholine and glutamate receptors modulate accumbal dopamine release.

This study determined the role of ventral tegmental area acetylcholine and glutamate receptors in modulating laterodorsal tegmentum stimulation-evoked dopamine efflux in the nucleus accumbens. Rapid changes in dopamine oxidation current were measured at carbon fiber microelectrodes using fixed potential amperometry in urethane anesthetized male mice. Intraventral tegmental area infusions of the muscarinic acetylcholine receptor antagonist scopolamine, the nicotinic acetylcholine receptor antagonist mecamylamine, or the ionotropic glutamate receptor antagonist kynurenate significantly diminished dopamine efflux in the nucleus accumbens evoked by brief electrical stimulation of the laterodorsal tegmentum.