Sex, but not juvenile stress, affects reversal learning and DRL performance following cocaine administration.

Introduction: Early adversity, impulsivity and sex all contribute to the risk of developing substance use disorder. Using rats, we examined how juvenile stress interacts with sex and cocaine to affect performance on a serial reversal task and a differential reinforcement of low rates 10 s (DRL10) task. The expression of dopamine-related proteins in several brain areas was also assessed.

Juvenile stress increases cocaine-induced impulsivity in female rats.

In humans, adverse childhood experiences are associated with an increased risk of developing a neuropsychiatric disorder. Changes in social behavior and cognitive function are hallmarks of numerous neuropsychiatric disorders. Here we examined the effects of exposure to variable stress during the juvenile period on social behavior, reward, and cognitive function (as measured in the 5-choice serial reaction time task (5CSRTT)) in rats.

Contribution of GABA receptor subunits to attention and social behavior.

Introduction: GABA dysfunction is associated with a number of psychiatric conditions including schizophrenia, autism and depression. Blocking cortical GABA receptors in rodents causes behavioral deficits, including impaired attention and sociability, that are consistent with the symptoms of these conditions. The subunit composition of GABA receptors is diverse and can affect receptor function.

Estradiol and luteinizing hormone regulate recognition memory following subchronic phencyclidine: Evidence for hippocampal GABA action.

The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia.

Decreasing GABA function within the medial prefrontal cortex or basolateral amygdala decreases sociability.

Introduction: Decreased sociability is a symptom of psychiatric conditions including autism-spectrum disorder and schizophrenia. Both of these conditions are associated with decreases in GABA function, particularly in the medial prefrontal cortex (PFC) and the basolateral amygdala (BLA); structures that are components of the social brain. Here, we determined if decreasing GABA transmission within either the PFC or the BLA decreases social behavior.

Effects of chronic inhibition of GABA synthesis on attention and impulse control.

Background: Cortical GABA regulates a number of cognitive functions including attention and working memory and is dysregulated in a number of psychiatric conditions. In schizophrenia for example, changes in GABA neurons [reduced expression of glutamic acid decarboxylase (GAD), parvalbumin (PV) and the GABA reuptake transporter (GAT1)] suggest reduced cortical GABA synthesis and release; these changes are hypothesized to cause the cognitive deficits observed in this disorder. The goals of this experiment were to determine whether chronically reducing GAD function within the rat PFC causes attention deficits and alterations in PV and GAT1 expression.

The 5-choice serial reaction time task: a task of attention and impulse control for rodents.

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. Test day challenges, modifications to the standard task, can be used to systematically tax the neural systems controlling either attention or impulse control. Importantly, these challenges have consistent effects on behavior across laboratories in intact animals and can reveal either enhancements or deficits in cognitive function that are not apparent when rats are only tested on the standard task.

Medial prefrontal cortex lesions impair decision-making on a rodent gambling task: reversal by D1 receptor antagonist administration.

Decision-making is a complex cognitive process that is impaired in a number of psychiatric disorders. In the laboratory, decision-making is frequently assessed using "gambling" tasks that are designed to simulate real-life decisions in terms of uncertainty, reward and punishment. Here, we investigate whether lesions of the medial prefrontal cortex (PFC) cause impairments in decision-making using a rodent gambling task (rGT).

Cue-induced conditioned activity does not incubate but is mediated by the basolateral amygdala.

Re-exposure to drug-associated cues causes significant drug craving in recovering addicts, which may precipitate relapse. In animal models of craving, drug-seeking responses for contingent delivery of drug-associated cues sensitizes or "incubates" across drug withdrawal. To date there is limited evidence supporting an incubation effect for behaviors mediated by non-contingent presentation of drug-associated cues.

Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task.

Attention deficits are a core cognitive symptom of schizophrenia; the neuropathology underlying these deficits is not known. Attention is regulated, at least in part, by the prefrontal cortex (PFC), a brain area in which pathology of γ-aminobutyric acid (GABA) neurons has been consistently observed in post-mortem analysis of the brains of people with schizophrenia. Specifically, expression of the 67-kD isoform of the GABA synthesis enzyme glutamic acid decarboxylase (GAD67) is reduced in parvalbumin-containing fast-spiking GABA interneurons.

Schizophrenia-like attentional deficits following blockade of prefrontal cortex GABAA receptors.

Attentional deficits are a core symptom of schizophrenia. Post-mortem analyses of the brains of schizophrenics reveal consistent abnormalities in γ-aminobutyric acid (GABA) interneurons indicative of reduced cortical GABA transmission, raising the possibility that this pathology contributes to attentional deficits. We examined whether blockade of prefrontal cortex (PFC) GABA(A) receptors with bicuculline (BMI) impairs attention in rats using the 5-choice serial reaction time task (5CSRTT).

Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats.

Background: Disruptions in perception and cognition are characteristic of psychiatric conditions such as schizophrenia. Studies of pharmacological agents that alter perception and cognition in humans might provide a better understanding of the brain substrates of these complex processes. One way to study these states in rodents is with tests that require attention and visual perception for correct performance.

Effects of antipsychotic drugs on MK-801-induced attentional and motivational deficits in rats.

Background: Attentional deficits that accompany schizophrenia are not effectively treated by available antipsychotic medications. Disruption of NMDA receptor function is often used to model aspects of this disorder in rodents. We used the 5-choice serial reaction time task (5CSRTT) to characterize attentional deficits caused by acute administration or withdrawal from chronic administration of the NMDA receptor antagonist MK-801, and determine if they are ameliorated by haloperidol or clozapine.

Attention deficits and hyperactivity following inhibition of cAMP-dependent protein kinase within the medial prefrontal cortex of rats.

Previous work demonstrates that microinjections of dopamine D1 receptor agonists and antagonists directly into the medial prefrontal cortex (mPFC) of rats can affect attention in the 5-choice serial reaction time task (5CSRTT), a rodent test analogous to the continuous performance task used to study attention in humans. These studies were designed to determine if intra-mPFC modulation of cAMP-dependent protein kinase (PKA), an intracellular target of D1 receptor stimulation, also affects attention. We examined the effects of localized microinfusions of the cAMP analog Sp-cAMPS (to activate PKA) or Rp-cAMPS (to inhibit PKA) in the 5CSRTT.

N-methylacetamide analog of salvinorin A: a highly potent and selective kappa-opioid receptor agonist with oral efficacy.

Several preclinical studies indicate that selective kappa-opioid receptor (KOR) antagonists have antidepressant-like effects, whereas KOR agonists have opposite effects, suggesting that each might be useful in the treatment of mood abnormalities. Salvinorin A (salvA) is a valuable KOR agonist for further study due to its high potency and receptor selectivity. However, it has short lasting effects in vivo and limited oral bioavailability, probably due to acetate metabolism.

Sensitivity of the five-choice serial reaction time task to the effects of various psychotropic drugs in Sprague-Dawley rats.

Background: Attentional deficits accompany many psychiatric disorders, underscoring the need for rodent models of attention to screen novel therapeutic agents and characterize the biological basis of attention. The five-choice serial reaction time task (5CSRTT) is one such model. Here, we characterized the effects of four standard psychotropic agents on performance in the 5CSRTT.

Alcohol-induced impulsivity in rats: an effect of cue salience?

Rationale: There is a common assumption that alcohol produces impulsive behaviors, thereby increasing the preference for immediate over delayed rewards. An alternative explanation, provided by alcohol myopia theory, is that alcohol alters attentional processes such that intoxicated individuals respond exclusively to the most salient cues in their environment.

Objectives: We tested these two hypotheses in rats using standard (impulsivity) and modified (cue salience) versions of the delayed reinforcement task.

Cocaine disrupts both behavioural inhibition and conditional discrimination in rats.

Rationale: Stimulant addicts exhibit increased behavioural disinhibition under the influence of the drug. In laboratory animals, however, the effects of amphetamine on behavioural disinhibition are equivocal, and the effects of cocaine have not been investigated.

Objectives: The current set of experiments was designed to test the effects of cocaine on behavioural disinhibition and to assess whether the possible impairments are due to deficits in conditional discrimination or attention.

Effects of chronic cocaine on impulsivity: relation to cortical serotonin mechanisms.

Drug addiction can be considered an impulse control disorder in that addicts exhibit increased impulsivity on both behavioural and self-report measures. We investigated whether chronic cocaine affects delay of gratification and/or behavioural disinhibition in rats using the delayed reinforcement and Go/No-go paradigms. Animals were treated with saline or cocaine (15 mg/kg) three times per day for 14 days; all behavioural tests occurred prior to daily injections.