Impulsive behaviour induced by both NMDA receptor antagonism and GABAA receptor activation in rat ventromedial prefrontal cortex.

Rationale: Previous work has demonstrated a profound effect of N-methyl-D: -aspartic acid receptor (NMDAR) antagonism in the infralimbic cortex (IL) to selectively elevate impulsive responding in a rodent reaction time paradigm. However, the mechanism underlying this effect is unclear.

Objectives: This series of experiments investigated the pharmacological basis of this effect in terms of excitatory and inhibitory neurotransmission.

Women's neuroethics? Why sex matters for neuroethics.

The Neuroethics Affinity Group of the American Society for Bioethics and Humanities (ASBH) met for the third time in October 2007 to review progress in the field of neuroethics and consider high-impact priorities for the future. Closely aligned with ASBH's own goals of recruiting junior scholars to bioethics and mentoring them to successful careers, the Neuroethics Affinity Group placed a call for new ideas to be presented at the Group meeting, specifically by junior attendees. One group responded with the idea to probe a new direction for neuroethics focused on the neuroscience of gender differences.

Opposing roles for 5-HT2A and 5-HT2C receptors in the nucleus accumbens on inhibitory response control in the 5-choice serial reaction time task.

Serotonin (5-HT) is thought to play an important role in the regulation of behavioral inhibition. Studies manipulating 5-HT function in the rodent brain indicate that 5-HT receptors regulate distinct forms of impulsive behavior, including impulsive responding in the 5-choice serial reaction time task (5CSRTT). The present study investigates the loci of effects mediated by 5-HT(2A) and 5-HT(2C) receptors in attention and inhibitory response control using microinfusions targeted at the nucleus accumbens (NAc), prelimbic cortex (PL) and infralimbic cortex (IL).

Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement.

Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release.

Behavioural pharmacology: 40+ years of progress, with a focus on glutamate receptors and cognition.

Behavioural pharmacology is an interdisciplinary field at the intersection of several research areas that ultimately lead to the development of drugs for clinical use and build understanding of how brain functions enable cognition and behaviour. In this article, the development of behavioural pharmacology in the UK is briefly surveyed, and the current status and success of the field is highlighted by the progress in our understanding of learning and memory that has resulted from discoveries in glutamate receptor pharmacology allied to theoretical and methodological advances in behavioural neuroscience. We describe the original breakthrough in terms of the role of NMDA receptors in hippocampal-mediated spatial learning and long-term potentiation, and review recent advances that demonstrate the involvement of glutamate receptor in working memory, recognition memory, stimulus-response learning and memory, and higher cognitive functions.

PDE10A inhibition reverses subchronic PCP-induced deficits in attentional set-shifting in rats.

Persistent suppression of N-methyl-d-aspartate (NMDA) receptor function produces enduring structural changes in neocortical and limbic regions in a pattern similar to changes reported in schizophrenia. This similarity suggests that chronic NMDA receptor antagonism in animals may represent a useful model of neurobiological and related cognitive deficits in schizophrenia. Schizophrenia is associated with impairments in frontal lobe-dependent cognitive functions, including working memory and attentional shifting.

Local glutamate receptor antagonism in the rat prefrontal cortex disrupts response inhibition in a visuospatial attentional task.

Rationale: Converging evidence implicates discrete areas of the rat prefrontal cortex in the modulation of different aspects of attention and executive control. Furthermore, the pharmacology of these behaviours has been relatively well characterised for the monoamine systems in a task of visuospatial attention, but it is not known how glutamate receptor antagonism in discrete regions of the prefrontal cortex affects attentional performance.

Objectives: To investigate the role of N-methyl-D-aspartate (NMDA) receptor antagonism in the prelimbic and infralimbic cortices (within the same animals) on performance of the five-choice serial reaction time task (5CSRTT), which assesses visuospatial attention and response inhibition.