Differential Contributions of Dopamine and Serotonin to Orbitofrontal Cortex Function in the Marmoset

We have shown previously that the inhibitory control functions of the orbitofrontal cortex (OFC) are disrupted by serotonin, but not dopamine depletions. However, both dopamine and serotonin terminals and receptors are present within the OFC and thus the aim of the present study was to determine the differential contributions of these neurotransmitters to orbitofrontal function. OFC and dopamine are involved in the process by which neutral stimuli take on reinforcing properties, by virtue of their prior association with reward, and guide behavior. Thus, we compared the performance of marmosets with dopaminergic or serotoninergic OFC depletions on a test of conditioned reinforcement. To further our understanding of serotonin in behavioral flexibility, the effect of these depletions was also compared on the extinction of a visual discrimination. Monkeys with serotonin depletions of the OFC displayed stimulus-bound responding on both tests of conditioned reinforcement and discrimination extinction suggesting that orbitofrontal serotonin plays a specific role in preventing competing, task irrelevant, salient stimuli from biasing responding. In contrast, monkeys with dopamine depletion were insensitive to conditioned reinforcers and displayed persistent responding in the absence of reward in extinction, a pattern of deficits that may reflect basic deficits in the associative processing of reward

Equine post-breeding endometritis: A review

The deposition of semen, bacteria and debris in the uterus of the mare after breeding normally induces a self-limiting endometritis. The resultant fluid and inflammatory products are cleared by 48 hours post cover. Mares that are susceptible to persistent post-breeding endometritis (PPBEM) have impaired uterine defence and clearance mechanisms, making them unable to resolve this inflammation within the normal time. This persists beyond 48 hours post-breeding and causes persistent fluid accumulation within the uterus. Mares with PPBEM have an increased rate of embryonic loss and a lower overall pregnancy rate than those without the condition. To enhance conception rates, mares at high risk need optimal breeding management as well as early diagnosis, followed by the most appropriate treatment. This article reviews the pathogenesis, diagnosis and treatment of PPBEM and the management of affected mares

Protection by the NDI1 Gene against Neurodegeneration in a Rotenone Rat Model of Parkinson's Disease

It is widely recognized that mitochondrial dysfunction, most notably defects in the NADH-quinone oxidoreductase (complex I), is closely related to the etiology of sporadic Parkinson's disease (PD). In fact, rotenone, a complex I inhibitor, has been used for establishing PD models both in vitro and in vivo. A rat model with chronic rotenone exposure seems to reproduce pathophysiological conditions of PD more closely than acute mouse models as manifested by neuronal cell death in the substantia nigra and Lewy body-like cytosolic aggregations. Using the rotenone rat model, we investigated the protective effects of alternative NADH dehydrogenase (Ndi1) which we previously demonstrated to act as a replacement for complex I both in vitro and in vivo. A single, unilateral injection of recombinant adeno-associated virus carrying the NDI1 gene into the vicinity of the substantia nigra resulted in expression of the Ndi1 protein in the entire substantia nigra of that side. It was clear that the introduction of the Ndi1 protein in the substantia nigra rendered resistance to the deleterious effects caused by rotenone exposure as assessed by the levels of tyrosine hydroxylase and dopamine. The presence of the Ndi1 protein also prevented cell death and oxidative damage to DNA in dopaminergic neurons observed in rotenone-treated rats. Unilateral protection also led to uni-directional rotation of the rotenone-exposed rats in the behavioral test. The present study shows, for the first time, the powerful neuroprotective effect offered by the Ndi1 enzyme in a rotenone rat model of PD

An investigation into aripiprazole's partial D(2) agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers

Rationale: Working memory impairments in schizophrenia have been attributed to dysfunction of the dorsolateral prefrontal cortex (DLPFC) which in turn may be due to low DLPFC dopamine innervation. Conventional antipsychotic drugs block DLPFC D2 receptors, and this may lead to further dysfunction and working memory impairments. Aripiprazole is a D2 receptor partial agonist hypothesised to enhance PFC dopamine functioning, possibly improving working memory. Objectives: We probed the implications of the partial D2 receptor agonist actions of aripiprazole within the DLPFC during working memory. Investigations were carried out in healthy volunteers to eliminate confounds of illness or medication status. Aripiprazole’s prefrontal actions were compared with the D2/5-HT2A blocker risperidone to separate aripiprazole’s unique prefrontal D2 agonist actions from its serotinergic and striatal D2 actions that it shares with risperidone. Method: A double-blind, placebo-controlled, parallel design was implemented. Participants received a single dose of either 5 mg aripiprazole, 1 mg risperidone or placebo before performing the n-back task whilst undergoing fMRI scanning. Results: Compared with placebo, the aripiprazole group demonstrated enhanced DLPFC activation associated with a trend for improved discriminability (d’) and speeded reaction times. In contrast to aripiprazole’s neural effects, the risperidone group demonstrated a trend for reduced DLPFC recruitment. Unexpectedly, the risperidone group demonstrated similar effects to aripiprazole on d’ and additionally had reduced errors of commission compared with placebo. Conclusion: Aripiprazole has unique DLPFC actions attributed to its prefrontal D2 agonist action. Risperidone’s serotinergic action that results in prefrontal dopamine release may have protected against any impairing effects of its prefrontal D2 blockade