Dissociable hippocampal and amygdalar D1-like receptor contribution to discriminated Pavlovian conditioned approach learning.

Pavlovian conditioning is an elementary form of reward-related behavioral adaptation. The mesolimbic dopamine system is widely considered to mediate critical aspects of reward-related learning. For example, initial acquisition of positively-reinforced operant behavior requires dopamine (DA) D1 receptor (D1R) activation in the basolateral amygdala (BLA), central nucleus of the amygdala (CeA), and the ventral subiculum (vSUB).

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action.

Opioid transmission and dysregulated prefrontal cortex (PFC) activity have both been implicated in the inhibitory-control deficits associated with addiction and binge-type eating disorders. What remains unknown, however, is whether endogenous opioid transmission within the PFC modulates inhibitory control. Here, we compared intra-PFC opioid manipulations with a monoamine manipulation (d-amphetamine), in two sucrose-reinforced tasks: progressive ratio (PR), which assays the motivational value of an incentive, and differential reinforcement of low response rates (DRLs), a test of inhibitory control.

Delay discounting for sucrose in alcohol-preferring and nonpreferring rats using a sipper tube within-sessions task.

Background: Delay discounting (DD) is a measure of impulsivity that quantifies preference for a small reward delivered immediately over a large reward delivered after a delay. It has been hypothesized that impulsivity is an endophenotype associated with increased risk for development of alcohol use disorders (AUDs); however, a causal role of impulsivity is difficult to determine with human studies. We tested this hypothesis by assessing the degree of DD present in alcohol-naïve rats selectively bred for either high- or low-alcohol preference.

The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats.

Low dose amphetamine (AMPH) and methylphenidate (MPH, Ritalin(®)) are the most widely prescribed and most effective pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Certain low, clinically relevant doses of MPH improve sustained attention and working memory in normal rats, in contrast to higher doses that impair cognitive ability and induce locomotor activity. However, the effects of AMPH of MPH on sustained attention and behavioral inhibition remain poorly characterized.

The clinical relevance of neuroplasticity in corticostriatal networks during operant learning.

Dopamine and glutamate serve crucial functions in neural plasticity, learning and memory, and addiction. Contemporary theories contend that these two, widely-distributed neurotransmitter systems play an integrative role in motivational and associative information processing. Combined signaling of these systems, particularly through the dopamine (DA) D1 and glutamate (Glu) N-methyl-d-aspartate receptors (NMDAR), triggers critical intracellular signaling cascades that lead to changes in chromatin structure, gene expression, synaptic plasticity, and ultimately behavior.

Adequacy of maternal iron status protects against behavioral, neuroanatomical, and growth deficits in fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) are the leading non-genetic cause of neurodevelopmental disability in children. Although alcohol is clearly teratogenic, environmental factors such as gravidity and socioeconomic status significantly modify individual FASD risk despite equivalent alcohol intake. An explanation for this variability could inform FASD prevention.

Operant learning requires NMDA-receptor activation in the anterior cingulate cortex and dorsomedial striatum, but not in the orbitofrontal cortex.

Previous research has shown that corticostriatal N-methyl-D-aspartate receptor (NMDAR) activation is necessary for operant learning. NMDAR activation induces plasticity-related intracellular signaling processes leading to gene expression, which are hypothesized to be important steps in codifying the content of learning. Operant learning induces immediate early gene (IEG) expression in key corticostriatal structures, namely the dorsomedial striatum (DMS), the orbitofrontal (OFC), and anterior cingulate cortices (ACC).

Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature death.

The longevity-assurance activity of the tumor suppressor p53 depends on the levels of Delta40p53 (p44), a short and naturally occurring isoform of the p53 gene. As such, increased dosage of p44 in the mouse leads to accelerated aging and short lifespan. Here we show that mice homozygous for a transgene encoding p44 (p44(+/+)) display cognitive decline and synaptic impairment early in life.

Intra-accumbens infusion of a muscarinic antagonist reduces food intake without altering the incentive properties of food-associated cues.

Previous work has implicated the cholinergic system in modulating feeding behavior; however, its specific function remains unclear. This work aims to characterize potential dissociations between the central cholinergic modulation of the incentive properties of food and food-associated cues, and consummatory behaviors. Three separate experiments demonstrated that intra-accumbens infusion of the muscarinic antagonist scopolamine 3 hr before the testing session significantly decreased food intake.

Is extinction the hallmark of operant discrimination? Reinforcement and S(Delta) effects.

Using a successive discrimination procedure with rats, three experiments investigated the contribution of reinforcement rate and amount of S(Delta) exposure on the acquisition of an operant discrimination. S(D) components and were always 2 min in length, while S(Delta) (extinction) components were either 1 min or 4 min in length; responses in S(D) were reinforced on one of four schedules. In Experiment 1, each of eight groups were exposed to one possible combination of rate of reinforcement and S(Delta) component length.

Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function.

Background: Low doses of psychostimulants, such as methylphenidate (MPH), are widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Surprisingly little is known about the neural mechanisms that underlie the behavioral/cognitive actions of these drugs. The prefrontal cortex (PFC) is implicated in ADHD.

Dissociating ventral and dorsal subicular dopamine D1 receptor involvement in instrumental learning, spontaneous motor behavior, and motivation.

A series of experiments investigating the role of dopamine D1 receptors in the ventral subiculum (vSUB) and dorsal subiculum (dSUB), 2 subregions of the hippocampal formation, found that D1 receptor antagonism (3.0 nmol/0.5 microl SCH-23390 bilaterally) in the vSUB impaired instrumental learning and performance, reduced break point in progressive ratio (PR) tests, and produced an intrasession decline in responding during test sessions, but had no effect on spontaneous motor or food-directed behavior.

The effect of REM sleep deprivation on motivation for food reward.

Prolonged sleep deprivation in rats produces a characteristic syndrome consisting of an increase in food intake yet a decrease in weight. Moreover, the increase in food intake generally precedes the weight loss, suggesting that sleep deprivation may affect appetitive behaviors. Using the multiple platform method to produce rapid eye movement (REM) sleep deprivation, we investigated the effect of REM sleep deprivation (REMSD) on motivation for food reward utilizing food-reinforced operant tasks.

AMPA/kainate, NMDA, and dopamine D1 receptor function in the nucleus accumbens core: a context-limited role in the encoding and consolidation of instrumental memory.

Neural integration of glutamate- and dopamine-coded signals within the nucleus accumbens (NAc) is a fundamental process governing cellular plasticity underlying reward-related learning. Intra-NAc core blockade of NMDA or D1 receptors in rats impairs instrumental learning (lever-pressing for sugar pellets), but it is not known during which phase of learning (acquisition or consolidation) these receptors are recruited, nor is it known what role AMPA/kainate receptors have in these processes. Here we show that pre-trial intra-NAc core administration of the NMDA, AMPA/KA, and D1 receptor antagonists AP-5 (1 microg/0.

Pigeons' choices between fixed-interval and random-interval schedules: utility of variability?

Pigeons' choosing between fixed-interval and random-interval schedules of reinforcement was investigated in three experiments using a discrete-trial procedure. In all three experiments, the random-interval schedule was generated by sampling a probability distribution at an interval (and in multiples of the interval) equal to that of the fixed-interval schedule. Thus the programmed delays to reinforcement on the random alternative were never shorter and were often longer than the fixed interval.

Central amygdalar and dorsal striatal NMDA receptor involvement in instrumental learning and spontaneous behavior.

Glutamate-coded signaling in corticostriatal circuits has been shown to be important in various forms of learning and memory. In the present study, the authors found that N-methyl-D-aspartate (NMDA) receptor antagonism in the central nucleus of the amygdala (CeA) and the posterior lateral striatum (PLS) impaired instrumental conditioning but had no effect in the anterior dorsal striatum. NMDA receptor antagonism in the CeA and PLS also affected spontaneous motor behavior and certain aspects of feeding.

Glutamate-mediated plasticity in corticostriatal networks: role in adaptive motor learning.

Little is known about how memories of new voluntary motor actions, also known as procedural memory, are formed at the molecular level. Our work examining acquisition of lever-pressing for food in rats has shown that activation of glutamate NMDA receptors, within broadly distributed but interconnected regions (e.g.

Interactions between the CB1 receptor agonist Delta 9-THC and the CB1 receptor antagonist SR-141716 in rats: open-field revisited.

This study examined the effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and the CB1 antagonist SR-141716 on open-field behaviors in male Sprague-Dawley rats. Animals were examined after administration of Delta(9)-THC alone (dose range: 0.3-5.