Orexin A-induced enhancement of attentional processing in rats: role of basal forebrain neurons

Orexins are neuropeptides released in multiple brain regions from neurons that originate within the lateral hypothalamus and contiguous perfornical area. The basal forebrain, a structure implicated in attentional processing, receives orexinergic inputs. Our previous work demonstrated that administration of an orexin-1 receptor antagonist, SB-334867, systemically or via infusion directly into the basal forebrain, can disrupt performance in a task that places explicit demands on attentional processing. Given that the orexin-1 receptor binds orexin A with high affinity, we tested whether orexin A could enhance attention in rats. Attentional performance was assessed using a task that required discrimination of variable duration visual signals from trials when no signal was presented. We also tested whether infusions of orexin A into the lateral ventricle could attenuate deficits following lesions of medial prefrontal cortical cholinergic projections that arise from the basal forebrain. Infusions of orexin A into the basal forebrain attenuated distracter-induced decreases in attentional performance. Orexin A attenuated deficits in lesioned animals when a visual distracter was presented. The present results support the view that orexin A can enhance attentional performance via actions in the basal forebrain and may be beneficial for some conditions characterized by attentional dysfunction due to disruption of cortical cholinergic inputs

Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala

Neuroplasticity may be defined as the ability of the central nervous system (CNS) to respond to changes in the internal and external environment and it is well established that some stimuli have the ability to facilitate or impair neuroplasticity depending on the pre-existing milieu. A classic example of a stimulus that can both facilitate and impair neuroplasticity is stress. Indeed, the ability of CNS to respond to acute stress is often dependent upon the prior stress history of the individual. While responses to acute stress are often viewed as adaptive in nature, stress reactivity in subjects with prior chronic stress experiences are often linked to neuropsychiatric disorders, including major depressive disorder, post-traumatic stress disorder (PTSD) and anxiety. In rodent studies, chronic stress exposure produces structural and functional alterations in the hippocampus and medial prefrontal cortex that are consistent across different types of stress paradigms. Conversely, the amygdala appears to exhibit differential structural and functional responses to stress that are dependent on a variety of factors, including the type of stressor performed and the duration of the stress paradigm. This is most evident in output measures including morphological analysis of amygdala neurons, measurement of glutamatergic tone in amygdalar subdivisions and the analysis of amygdala-centric behaviors. Accordingly, this review will provide an overview of the effects of stress on the structural and functional plasticity of the rodent amygdala, especially in relation to the differential effects of repeated or chronic stress paradigms on dendritic architecture, neurochemistry of the glutamatergic system and behavior

Dopaminergic regulation of orexin neurons

Orexin/hypocretin neurons in the lateral hypothalamus and adjacent perifornical area (LH/PFA) innervate midbrain dopamine (DA) neurons that project to corticolimbic sites and subserve psychostimulant-induced locomotor activity. However, it is not known whether dopamine neurons in turn regulate the activity of orexin cells. We examined the ability of dopamine agonists to activate orexin neurons in the rat, as reflected by induction of Fos. The mixed dopamine agonist apomorphine increased Fos expression in orexin cells, with a greater effect on orexin neurons located medial to the fornix. Both the selective D1-like agonist, A-77636, and the D2-like agonist, quinpirole, also induced Fos in orexin cells, suggesting that stimulation of either receptor subtype is sufficient to activate orexin neurons. Consistent with this finding, combined SCH 23390 (D1 antagonist)–haloperidol (D2 antagonist) pretreatment blocked apomorphine-induced activation of medial as well as lateral orexin neurons; in contrast, pretreatment with either the D1-like or D2-like antagonists alone did not attenuate apomorphine-induced activation of medial orexin cells. In situ hybridization histochemistry revealed that LH/PFA cells rarely express mRNAs encoding dopamine receptors, suggesting that orexin cells are transsynaptically activated by apomorphine. We therefore lesioned the nucleus accumbens, a site known to regulate orexin cells, but this treatment did not alter apomorphine-elicited activation of medial or lateral orexin neurons. Interestingly, apomorphine failed to activate orexin cells in isoflurane-anaesthetized animals. These data suggest that apomorphine-induced arousal but not accumbens-mediated hyperactivity is required for dopamine to transsynaptically activate orexin neurons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71513/1/j.1460-9568.2005.04121.x.pd