The dopamine projection to the nucleus accumbens has been implicated in behaviors directed toward acquisition and consumption of natural rewards. neurochemical studies that established this link made time-averaged measurements over minutes, so precise temporal relationship between changes these is not known. To resolve this, we sampled every 100 msec using fast-scan cyclic voltammetry at carbon-fiber microelectrodes rats trained press a lever for sucrose. Cues signal opportunity respond...

Trodusquemine (MSI-1436) causes rapid and reversible weight loss in genetic models of obesity. To better predict the potential effects trodusquemine clinic, we investigated treatment a murine model diet-induced obesity (DIO). suppressed appetite, reduced body (BW) fat-specific manner, improved plasma insulin leptin levels mice. Screening assays revealed that selectively inhibited protein-tyrosine phosphatase 1B (PTP1B), key enzyme regulating signaling. significantly enhanced...

Abstract Phasic changes in dopamine activity play a critical role learning and goal‐directed behavior. Unpredicted reward reward‐predictive cues evoke phasic increases the firing rate of majority midbrain neurons – results that predict uniformly broadcast concentration throughout striatum. However, measurement during has cast doubt on this prediction. We systematically measured four striatal subregions [nucleus accumbens shell core (Core), dorsomedial (DMS) dorsolateral striatum] response to...

Brief, high-concentration (phasic) spikes in nucleus accumbens dopamine critically participate aspects of food reward. Although physiological state (e.g., hunger, satiety) and associated hormones are known to affect tone general, whether they modulate food-evoked, phasic specifically is unknown. Here, we used fast-scan cyclic voltammetry awake, behaving rats record evoked by delivery sugar pellets while pharmacologically manipulating central receptors for the gut “hunger” hormone ghrelin....

Drugs of abuse hijack brain-reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear be amphetamine (AMPH) related analogs, which are proposed instead disrupt normal patterns neurotransmission depleting vesicular stores promoting nonexocytotic efflux via reverse transport. This mechanism AMPH action, though, is inconsistent its...

Adaptive motivated behavior requires rapid discrimination between beneficial and harmful stimuli. Such leads to the generation of either an approach or rejection response, as appropriate, enables organisms maximize reward minimize punishment. Classically, nucleus accumbens (NAc) dopamine projection it are considered integral part brain's circuit, i.e., they direct consumption behaviors underlie positive reinforcement. This reward-centered framing ignores important evidence about role this...

Mesolimbic dopamine neurons fire in both tonic and phasic modes resulting detectable extracellular levels of the nucleus accumbens (NAc). In past, different techniques have targeted NAc to establish a basal concentration. this study, we used vivo fast scan cyclic voltammetry (FSCV) awake, freely moving rats. The experiments were primarily designed capture changes caused by firing - that is, measurement 'transients'. These FSCV measurements revealed for first time spontaneous transients...

The contribution of dopamine (DA) to locomotor control is traditionally attributed ascending dopaminergic projections from the substantia nigra pars compacta and ventral tegmental area basal ganglia, which in turn project down mesencephalic region (MLR), a brainstem controlling locomotion vertebrates. However, innervation pedunculopontine nucleus, considered part MLR, was recently identified monkey. origin role this input are unknown. We addressed these questions vertebrate, lamprey. Here we...

The development of diet-induced obesity (DIO) can potently alter multiple aspects dopamine signaling, including transporter (DAT) expression and reuptake. However, the time-course changes in DAT function whether such are dependent upon DIO remains unresolved. Here, we fed rats a high (HFD) or low (LFD) fat diet for 2 6 weeks. Following exposure, were anesthetized with urethane striatal was assessed by electrically stimulating cell bodies ventral tegmental area (VTA) recording resultant...

Glucagon-like peptide-1 receptor (GLP-1R) activation in the nucleus accumbens (NAc) core is pharmacologically and physiologically relevant for regulating palatable food intake. Here, we assess whether GLP-1R signaling NAc of rats modulates GABAergic medium spiny neurons (MSNs) through presynaptic-glutamatergic and/or presynaptic-dopaminergic to control feeding. First, ex vivo fast-scan cyclic voltammetry showed that agonist exendin-4 (Ex-4) does not alter dopamine release core. Instead,...

Significance In vertebrates, the contribution of dopamine neurons to locomotor control is traditionally attributed their ascending projections basal ganglia that, in turn, project down brainstem networks. We recently discovered lampreys that networks receive a direct descending dopaminergic input increases output. Here, we show this pathway conserved higher vertebrates. found released salamander networks, together with reticulospinal cell activation, known trigger locomotion. Dopamine rat...

Abstract Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism's ability to track and secure natural rewards, but may also contribute the compulsive nature drug addiction. Here, we examined activity individual nucleus accumbens (NAc) neurons during autoshaping paradigm. One conditioned stimulus (CS+, a retractable lever presented for 10 s) was immediately followed by delivery 45‐mg sucrose pellet food receptacle, while another...

Abstract Drug seeking is significantly regulated by drug‐associated cues and associative learning between environmental cocaine reward mediated dopamine transmission within the nucleus accumbens (NAc). However, during early acquisition of a cue–cocaine association has never been assessed because technical difficulties associated with resolving cue‐evoked cocaine‐evoked release same conditioning trial. Here, we used fast‐scan cyclic voltammetry to measure sub‐second fluctuations in...

Cues that have been paired with food evoke dopamine in nucleus accumbens (NAc) and drive approach behavior. This cue-evoked signaling could contribute to overconsumption of food. One manner which individuals try restrict caloric intake is through the consumption foods containing artificial (non-nutritive) sweeteners. We were interested whether cues a non-nutritive sweetener (saccharin) would similar release as nutritive (sucrose). trained food-restricted rats associate distinct sucrose or...

Significance Associating environmental cues with their outcomes occurs through multiple strategies relying on different neural substrates. Unpredicted reward evokes dopamine release, which also develops to predictive cues, suggesting that signals arise only after extensive pairings of appetitive outcomes. However, recent work suggests may contribute model-based learning, does not require and be experienced in tandem. Taking advantage the value a hypertonic sodium solution, radically...

Environmental stimuli that signal food availability hold powerful sway over motivated behavior and promote feeding, in part, by activating the mesolimbic system. These food-predictive cues evoke brief (phasic) changes nucleus accumbens (NAc) dopamine concentration activity of individual NAc neurons. Phasic fluctuations signaling have been directly linked to goal-directed behaviors, including behaviors elicited cues. Food-seeking is also strongly influenced physiological state (i.e., hunger...