No abstract

Dopamine D(3) antagonism combined with serotonin 5-HT(1A) and 5-HT(2A) receptor occupancy may represent a novel paradigm for developing innovative antipsychotics. The unique pharmacological features of 5i are a high affinity for dopamine D(3), serotonin 5-HT(1A) and 5-HT(2A) receptors, together with a low affinity for dopamine D(2) receptors (to minimize extrapyramidal side effects), serotonin 5-HT(2C) receptors (to reduce the risk of obesity under chronic treatment), and for hERG channels (to reduce incidence of torsade des pointes). Pharmacological and biochemical data, including specific c-fos expression in mesocorticolimbic areas, confirmed an atypical antipsychotic profile of 5i in vivo, characterized by the absence of catalepsy at antipsychotic dose.

The contribution of the amygdala to neuropathic pain processing in animals has not been clearly acknowledged. To assess the relative contribution of amygdala GABA-A receptors in mediating sensory-discriminative and affective-motivational pain components, the GABA-A receptor agonist muscimol and the antagonist bicuculline (both 10-25 ng/microl) were administered by acute bilateral injection directly into the central amygdala in rats with a chronic constriction injury (CCI). Escape/avoidance behaviour reflecting the affective-motivational dimension of pain was measured using a light/dark chamber in combination with suprathreshold nociceptive stimulation, and was defined as a shift from the 'non-aversive' dark area of the chamber to the 'aversive' light area. Hindpaw mechanical allodynia and mechanical hyperalgesia thresholds reflecting the sensory-discriminative dimension of pain were determined prior to and following escape/avoidance testing. Muscimol administration into the amygdala attenuated escape/avoidance behaviour and reversed hindpaw mechanical hypersensitivity in CCI rats; the magnitude of reduction in escape/avoidance behaviour was 2- to 3-fold greater than mechanical allodynia. Surprisingly, administration of bicuculline also attenuated escape/avoidance behaviour but had no effect on nociceptive behaviours. The muscimol-induced reversal of hindpaw mechanical hypersensitivity was completely blocked by co-administration of bicuculline, in contrast to escape/avoidance behaviour. Motility behaviour was unaffected by injection of either drug as determined in the open field test. Thus, amygdala GABA-A receptors appear to play an important role in sensory and especially affective pain processing in neuropathic rats. Furthermore, after nerve injury reflex nociceptive behaviours appear to be under tonic control by descending inputs, which originate from or are modulated within the amygdala.

No abstract

Throughout the past decade it has been recognized that dopaminergic medication administered to remedy motor symptoms in Parkinson's disease is associated with an enhanced risk for impulse control disorders and related compulsive behaviors such as hobbyism, punding, and the dopamine dysregulation syndrome. These complications are relatively frequent, affecting 6-15.5% of patients, and they most often appear, or worsen, after initiation of dopaminergic therapy or dosage increase. Recently, impulse control disorders have also been associated with subthalamic nucleus deep brain stimulation. Here we present a systematic overview of literature published between 2000 and January 2013 reporting impulse control disorders in Parkinson's disease. We consider prevalence rates and discuss the functional neuroanatomy, the impact of dopamine-serotonin interactions, and the cognitive symptomatology associated with impulse control disorders in Parkinson's disease. Finally, perspectives for future research and management of impulse control disorders in Parkinson's disease are discussed.

No abstract

No abstract

Male Wistar rats were tested in the Morris water maze task 1 week after 6, 9, or 12 min of transient global ischemia. The 9-min and 12-min ischemia groups were significantly impaired in the acquisition and the reversal experiment. A systematic counting of CA1 neurons in the whole hippocampal formation revealed a unilateral number of CA1 neurons of 286,000 in the sham group, of which 2/3 were located in the dorsal hippocampus. The ischemia groups showed a significant decline in the number of dorsal CA1 neurons, whereas only the 12-min ischemia group showed a significant but minor decline (10%-15%) in the number of ventral CA1 neurons. A correlation analysis showed that the escape distance declined with increasing number of viable CA1 neurons, but poor correlation coefficients were obtained. Thus, some of the ischemic rats with even very few viable CA1 neurons in the dorsal hippocampus were capable of performing this spatial learning task at sham-group level.