John J Renger9
Pete H Hutson7
Christopher J Winrow7
Lihang Yao7
9John J Renger
7Pete H Hutson
7Christopher J Winrow
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Orexin is a key neurotransmitter of central arousal and reward circuits in the CNS. Two receptors respond to orexin signaling, Orexin 1 Receptor (OX1R) and Orexin 2 Receptor (OX2R) with partially overlapping brain distributions. Genetic and pharmacological studies suggest orexin receptor antagonists could provide therapeutic benefit for insomnia and other(More)
Repeated exposure to psychostimulant drugs produces long-lasting changes in dendritic structure, presumably reflecting a reorganization in patterns of synaptic connectivity, in brain regions that mediate the psychomotor activating and incentive motivational effects of these drugs, including the nucleus accumbens and prefrontal cortex. However, repeated(More)
A central premise of a number of theories of addiction is that discrete environmental stimuli repeatedly paired with drugs of abuse acquire incentive salience as a result of Pavlovian learning. There is, however, no unequivocal evidence supporting this assumption. Thus, we employed a Pavlovian conditioning procedure known to imbue non-drug reinforcers with(More)
Multiple studies indicate that N-methyl-D-aspartate (NMDA) receptor hypofunction underlies some of the deficits associated with schizophrenia. One approach for improving NMDA receptor function is to enhance occupancy of the glycine modulatory site on the NMDA receptor by increasing the availability of the endogenous coagonists D-serine. Here, we(More)
The subthalamic nucleus (STN) is traditionally thought of as part of a system involved in motor control but recent evidence suggests that it may also play a role in other psychological processes. Here we examined the effects of STN lesions on two measures of impulsivity and found that STN lesions increased 'impulsive action' (produced behavioral(More)
Current treatments for insomnia, such as zolpidem (Ambien) and eszopiclone (Lunesta), are γ-aminobutyric acid type A (GABAA)-positive allosteric modulators that carry a number of side effects including the potential to disrupt cognition. In an effort to develop better tolerated medicines, we have identified dual orexin 1 and 2 receptor antagonists (DORAs),(More)
Dual orexin receptor antagonists (DORAs) induce sleep by blocking orexin 1 and orexin 2 receptor-mediated activities responsible for regulating wakefulness. DORAs represent a potential alternative mechanism to the current standard of care that includes the γ-aminobutyric acid (GABA)A receptor-positive allosteric modulators, eszopiclone and zolpidem. This(More)
T-type calcium channels are important in burst firing and expressed in brain regions implicated in schizophrenia. Therefore, we examined the effects of novel selective T-type calcium channel antagonists in preclinical assays predictive of antipsychotic-like activity. TTA-A2 blocked the psychostimulant effects of amphetamine and MK-801 and decreased(More)
D-amino acid oxidase (DAAO) is a flavoenzyme that degrades D-amino acids through the process of oxidative deamination. DAAO regulation of D-amino acid levels has been associated with several physiological processes ranging from hormone secretion to synaptic transmission and cognition. Recent genetic studies have identified a mutation on chromosome 13 in(More)
When administered in a novel environment relatively low doses of amphetamine induce c-fos mRNA in the subthalamic nucleus (STN) and in preproenkephalin mRNA-containing (ENK+) neurons in the caudate-putamen (CPu). When administered at home, however, low doses of amphetamine do not produce these effects. Environmental novelty also facilitates the behavioral(More)