Cocaine Seeking And Taking Are Oppositely Regulated By Dopamine.

In some individuals, drug-associated cues subsume potent control of behavior, such as the elicitation of drug craving and automatized drug use. The intensity of this cue reactivity is highly predictive of relapse and other clinical outcomes in substance use disorders. It has been postulated that this cue reactivity is driven by augmentation of dopamine release over the course of chronic drug use.

Absence of NMDA receptors in dopamine neurons attenuates dopamine release but not conditioned approach during Pavlovian conditioning.

During Pavlovian conditioning, phasic dopamine (DA) responses emerge to reward-predictive stimuli as the subject learns to anticipate reward delivery. This observation has led to the hypothesis that phasic dopamine signaling is important for learning. To assess the ability of mice to develop anticipatory behavior and to characterize the contribution of dopamine, we used a food-reinforced Pavlovian conditioning paradigm.

Chronic microsensors for longitudinal, subsecond dopamine detection in behaving animals.

Neurotransmission operates on a millisecond timescale but is changed by normal experience or neuropathology over days to months. Despite the importance of long-term neurotransmitter dynamics, no technique exists to track these changes in a subject from day to day over extended periods of time. Here we describe and characterize a microsensor that can detect the neurotransmitter dopamine with subsecond temporal resolution over months in vivo in rats and mice.

Intraventricular insulin and leptin reverse place preference conditioned with high-fat diet in rats.

The authors hypothesized that insulin and leptin, hormones that convey metabolic and energy balance status to the central nervous system (CNS), decrease the reward value of food, as assessed by conditioned place preference (CPP). CPP to high-fat diet was blocked in ad-lib fed rats given intraventricular insulin or leptin throughout training and test or acutely before the test. Insulin or leptin given only during the training period did not block CPP.

Inactivation of the DMH selectively inhibits the ACTH and corticosterone responses to hypoglycemia.

We have previously reported that repeated bouts of insulin-induced hypoglycemia (IIH) in the rat result in blunted activation of the paraventricular, arcuate, and dorsomedial hypothalamic (DMH) nuclei. Because DMH activation has been implicated in the sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to stressors, we hypothesized that its blunted activation may play a role in the impaired counterregulatory response that is also observed with repeated bouts of IIH. In the present study, we evaluated the role of normal DMH activation in the counterregulatory response to a single bout of IIH.

Inactivation of the PVN during hypoglycemia partially simulates hypoglycemia-associated autonomic failure.

The anatomic connections of the paraventricular nucleus of the hypothalamus (PVN) are such that it is ideally situated to modulate and/or control autonomic responses to a variety of stressors, including hypoglycemia. In our experimental model of hypoglycemia-associated autonomic failure (HAAF), a syndrome in which the counterregulatory response to hypoglycemia is partially compromised via unknown mechanisms, activation of the PVN is blunted (15). We hypothesized that this blunted PVN activation during HAAF may be sufficient to cause the impaired counterregulatory response.

Food restriction modulates amphetamine-conditioned place preference and nucleus accumbens dopamine release in the rat.

Food restriction has been shown to increase self-administration of psychostimulants, including cocaine and amphetamine (AMPH). Consistent with this, food-restricted rats are more sensitized to the rewarding effects of cocaine as measured by conditioned place preference (CPP). This study investigated whether moderate food restriction in rats (15 g/day) results in an increased CPP, relative to ad libitum-fed controls, to a second psychostimulant, AMPH.