dcc Haploinsufficiency results in blunted sensitivity to cocaine enhancement of reward seeking.

Mesocortical dopamine connectivity continues to mature during adolescence. This protracted development confers increased vulnerability for environmental and genetic factors to disrupt mesocortical wiring and subsequently influence responses to drugs of abuse in adulthood. The netrin-1 receptor, DCC, orchestrates medial prefrontal cortex dopamine input during adolescence and dictates the functional organization of local circuitry.

Nucleus Accumbens and Posterior Amygdala Mediate Cue-Triggered Alcohol Seeking and Suppress Behavior During the Omission of Alcohol-Predictive Cues.

Neurobiological mechanisms that influence behavior in the presence of alcohol-associated stimuli involve processes that organize behavior during the presence of these cues, and separately, regulation of behavior in their absence. However, little is known about anatomical structures that might mediate this regulation. Here we examined nucleus accumbens shell (AcbSh) as a possible neural substrate mediating behavior modulation triggered by the presence and absence of alcohol-associated environmental cues and contexts.

Integration of neural networks activated by amphetamine in females with different estrogen levels: a functional imaging study in awake rats.

Previous studies demonstrate that schizophrenia symptomatology in women is dependent upon estrogen levels. Estrogen has beneficial properties when administered in conjunction with antipsychotics, and estrogen also alters, in rats, dopamine neurotransmission, which is a common target of all antipsychotic medications, suggesting a possible interaction between the two. The aim of the current study was to investigate this possible interaction using functional magnetic resonance imaging in awake, female rats.

Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats.

The infralimbic medial prefrontal cortex (IL) has been posited as a common node in distinct neural circuits that mediate the extinction of appetitive and aversive conditioning. However, appetitive extinction is typically assessed using instrumental conditioning procedures, whereas the extinction of aversive conditioning is customarily studied using Pavlovian assays. The role of the IL in the extinction of appetitive Pavlovian conditioning remains underexplored.

The effect of probability discounting on reward seeking: a three-dimensional perspective.

Rats will work for electrical stimulation of the medial forebrain bundle. The rewarding effect arises from the volleys of action potentials fired by the stimulation and subsequent spatio-temporal integration of their post-synpatic impact. The proportion of time allocated to self-stimulation depends on the intensity of the rewarding effect as well as on other key determinants of decision-making, such as subjective opportunity costs and reward probability.

Leptin modulates the late fever response to LPS in diet-induced obese animals.

Leptin is an important modulator of both inflammation and energy homeostasis, making it a key interface between the inflammatory response to pathogenic stimuli and the energy status of the host. In previous studies we demonstrated that sickness responses to systemic immune challenge, including fever, are significantly exacerbated in diet induced obese animals. To investigate whether this exacerbation is functionally linked to the obesity associated increase in circulating levels of leptin, a species-specific leptin antiserum (LAS) was used to neutralize endogenous leptin in diet-induced obese adult male Wistar rats treated with a single intraperitoneal (i.

Pavlovian-conditioned alcohol-seeking behavior in rats is invigorated by the interaction between discrete and contextual alcohol cues: implications for relapse.

Introduction: Drug craving can be independently stimulated by cues that are directly associated with drug intake (discrete drug cues), as well as by environmental contexts in which drug use occurs (contextual drug cues). We tested the hypothesis that the context in which a discrete alcohol-predictive cue is experienced can influence how robustly that cue stimulates alcohol-seeking behavior.

Methods: Male, Long-Evans rats received Pavlovian discrimination training (PDT) sessions in which one conditioned stimulus (CS+; 16 trials/session) was paired with ethanol (0.

A procedure to study the effect of prolonged food restriction on heroin seeking in abstinent rats.

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during abstinence. Moreover, various environmental challenges can exacerbate this effect, as well as increase ongoing drug intake. The procedure we describe here highlights the impact of a common environmental challenge, food restriction, on drug craving that is expressed as an augmentation of drug seeking in abstinent rats.

A new view of the effect of dopamine receptor antagonism on operant performance for rewarding brain stimulation in the rat.

Rationale: Previous studies of neuroleptic challenges to intracranial self-stimulation (ICSS) employed two-dimensional (2D) measurements (curve shifts). Results so obtained are ambiguous with regard to the stage of neural processing at which the drug produces its performance-altering effect. We substituted a three-dimensional (3D) method that measures reward-seeking as a function of both the strength and cost of reward.

Clitoral anesthesia disrupts paced copulation in the female rat.

Clitoral stimulation produced by sexual contact with a partner or during manual stimulation is associated with pleasure in humans, and produces conditioned place preference in rats. The present experiment investigated the effect of blocking genitosensory stimulation of the clitoris with lidocaine during copulation in female rats on a measure of female sexual motivation: pacing behavior. Sexually naïve, ovariectomized female rats were treated with 10μg estradiol benzoate 48h and 500μg progesterone 4h prior to a 30-min copulatory trial with a sexually vigorous stimulus male scheduled every 4days.

Blocking dopamine d1-like receptors attenuates context-induced renewal of pavlovian-conditioned alcohol-seeking in rats.

Background: Environmental contexts associated with drug use can trigger craving in humans and the renewal of drug-seeking behaviors in animals. Here, we tested the hypothesis that context-induced renewal of Pavlovian-conditioned alcohol-seeking is mediated by dopamine.

Methods: Male, Long-Evans rats were trained to discriminate between two, 10-second, auditory conditioned stimuli.

Validation and extension of the reward-mountain model.

The reward-mountain model relates the vigor of reward seeking to the strength and cost of reward. Application of this model provides information about the stage of processing at which manipulations such as drug administration, lesions, deprivation states, and optogenetic interventions act to alter reward seeking. The model has been updated by incorporation of new information about frequency following in the directly stimulated neurons responsible for brain stimulation reward and about the function that maps objective opportunity costs into subjective ones.

The effects of dietary saturated fat on basal hypothalamic neuroinflammation in rats.

Recent evidence has demonstrated that consumption of high fat diets can trigger brain inflammation and subsequent injury in the absence of any peripheral inflammatory signaling. Here we sought to investigate whether a link exists between the concentration of highly saturated fats in the diet and the development of inflammation in the brain of rats and, whether the source of the saturated fat was an important factor in this process. Adult male rats had access to diets with a moderate level of total fat (32% of calories as fat) varying in level of saturated fat [low (20%) vs high (>60%)] and its source (butter or coconut oil).

Sexual experience blocks the ability of clitoral stimulation to induce a conditioned place preference in the rat.

We have previously established the rewarding value of clitoral stimulation (CLS) through the demonstration that manual, distributed, CLS induces a significant conditioned place preference (CPP) and conditioned partner preference in naïve, hormonally primed and non-hormonally primed rats. The present experiment asks whether previous sexual experience might inhibit the ability of clitoral stimulation to induce a conditioned place preference. Female Long-Evans rats were ovariectomized and treated with 10 μg of estradiol benzoate (EB) 48 h and 500 μg of progesterone (P) 4h prior to receiving either 0, 1, or 5 consecutive copulatory sessions with a sexually vigorous male.

Context alters the ability of clitoral stimulation to induce a sexually-conditioned partner preference in the rat.

We have shown previously that clitoral stimulation (CLS) of female rats induces significant conditioned place preference (CPP), indicating that it is rewarding. The present study asked whether CLS could induce a conditioned partner preference. In the first experiment, sexually naïve females received 10 alternating trials of CLS and No-CLS in the presence of a male rat behind a wire-mesh screen.

Temporary inactivation of the dorsal entorhinal cortex impairs acquisition and retrieval of spatial information.

We tested the effects of temporary inactivation of the dorsal entorhinal cortex on spatial discrimination using a conditioned cue preference (CCP) paradigm. The three phases of the procedure were: pre-exposure: unreinforced exploration of the center platform and two adjacent arms of an eight-arm radial maze; training: rats were confined to the ends of the two arms on alternate days - one arm always contained food and the other never contained food; testing: unreinforced exploration of the center platform and the two arms. Rats that received bilateral infusions of saline into the dorsal entorhinal cortex before the training trials or before the test trial spent significantly more time in the arm that previously contained food than in the arm that never contained food, demonstrating that they had acquired and were able to express information that discriminated between the two adjacent maze arms.

Rattus Psychologicus: construction of preferences by self-stimulating rats.

Behavioral economists have proposed that human preferences are constructed during their elicitation and are thus influenced by the elicitation procedure. For example, different preferences are expressed when options are encountered one at a time or concurrently. This phenomenon has been attributed to differences in the "evaluability" of a particular attribute when comparison to an option with a different value of this attribute is or is not available.

Incidental (unreinforced) and reinforced spatial learning in rats with ventral and dorsal lesions of the hippocampus.

We investigated whether the ventral and dorsal hippocampus were differentially involved in incidental spatial learning. Rats with ventral and dorsal hippocampal lesions were tested on an unreinforced test of spatial memory that takes advantage of their natural propensity to explore novelty. Rats were presented with two copies of an identical object in a large circular open field arena.

Patterns of retrograde amnesia for recent and remote incidental spatial learning in rats.

A non-navigational test of incidental spatial learning was used to determine whether hippocampal damage causes temporally-graded retrograde amnesia (TGRA) for allocentric-spatial information. Rats were exposed to two identical objects in a circular open field for 7 min on seven consecutive days. In the 1-3 days after the last day of familiarization, rats received neurotoxic lesions of the hippocampal formation (HPC) or sham lesions.

A limited role for the hippocampus in the modulation of novel-object preference by contextual cues.

Recent evidence suggests that rats require an intact hippocampus in order to recognize familiar objects when they encounter them again in a different context. The two experiments reported here further examined how changes in context affect rats' performance on the novel-object preference (NOP) test of object-recognition memory, and how those effects interact with the effects of HPC damage. Rats with HPC lesions and control rats received NOP testing in either the same context in which they had previously encountered sample objects, or in a different but equally familiar context.

The reinforcement mountain: allocation of behavior as a function of the rate and intensity of rewarding brain stimulation.

The single-operant matching law has been used to describe the relationship between time allocated to pursuit of brain stimulation reward (BSR) and the obtained rate of reinforcement. We generalize this relationship to a third dimension by including the strength of the stimulation (the number of pulses per train) as an independent dimension, and we dub the resulting 3-dimensional structure "the reinforcement mountain." The validity of generalizing the single-operant matching law in this way was assessed by determining the changes in the position of the mountain produced by increasing the stimulation current or the train duration.

Potentiation of intracranial self-stimulation during prolonged subcutaneous infusion of cocaine.

Subcutaneous administration of cocaine yields a longer duration of action than administration via the intraperitoneal or intravenous routes. However, cocaine is a powerful vasoconstrictor, and thus injection of this drug at a single subcutaneous locus entails significant risk of necrotic skin lesions. This paper introduces a new method for subcutaneous administration of cocaine that reduces the probability of dermonecrosis by dispersing the drug under a large area of skin.

Predictable and unpredictable rewards produce similar changes in dopamine tone.

Unpredicted rewards trigger more vigorous phasic responses in midbrain dopamine (DA) neurons than predicted rewards. However, recent evidence suggests that reward predictability may fail to influence DA signaling over longer scales: In rats passively receiving rewarding electrical brain stimulation, the concentration of DA in dialysate obtained from nucleus accumbens probes was similar regardless of whether reward onset was predictable (G. Hernandez et al.

Perirhinal cortex damage and anterograde object-recognition in rats after long retention intervals.

Damage to the perirhinal cortex (PRh) in rats impairs anterograde object-recognition memory after retention intervals of up to several hours, but there is little direct evidence to link PRh function to object-recognition abilities after substantially longer intervals that span several days or weeks. We assessed the effects of PRh lesions on anterograde object recognition using a novel-object preference test, with retention intervals lasting 24 h and 3 weeks. The rats received multiple exposures to the sample object during the learning phase--5 min per day on 5 consecutive days.

Prolonged rewarding stimulation of the rat medial forebrain bundle: neurochemical and behavioral consequences.

Extracellular dopamine levels were measured in the rat nucleus accumbens by means of in vivo microdialysis. Delivery of rewarding medial forebrain bundle stimulation at a low rate (5 trains/min) produced a sustained elevation of dopamine levels, regardless of whether train onset was predictable. When the rate of train delivery was increased to 40 trains/min, dopamine levels rose rapidly during the first 40 min but then declined toward the baseline range.