Prostaglandin (PG)s D2 and E2 are the major arachidonic acid metabolites in the mammalian brain. PGD synthase, the enzyme that produces PGD2 in the brain, is mainly localized in the arachnoid membrane and choroid plexus. It is secreted into the cerebrospinal fluid and circulates in the brain through the ventricular system. PGD2 induces sleep by acting on the surface of the ventro-medial region of the rostral basal forebrain, the signal of which is probably transmitted into the brain parenchyma by adenosine via adenosine A2a receptors. Fos expression experiments suggest that PGD2 inhibits histaminergic arousal neurons of the tuberomammillary nucleus (TMN) in the posterior hypothalamus by activating inhibitory neurons in the ventrolateral preoptic area (VLPO). However, PGE2 causes wakefulness by activating arousal neurons in the TMN via AMPA type excitatory amino acid receptors. Therefore, PGD2, acting as a sleep-inducer, and PGE2, acting as a wakefulness-promoter, jointly regulate the generation of sleep and wakefulness in the mammalian brain.
There have been many efforts to develop novel antipsychotic drugs with improved clinical efficacy and reduced side effects such as extrapyramidal side effects and hyperprolactinemia. Recent evidences from studies on the effects of novel antipsychotic drugs such as clozapine on neurotransmitter receptors are prompting reconsideration of the dopaminergic hypothesis of schizophrenia. This paper gives an overview of the current understanding, including our data, of the effects of several antipsychotics on dopamine receptor subtypes. The recent cloning of dopamine receptors has revealed that multiple dopamine receptor subtypes are generated from at least five distinct dopamine receptor genes. Aripiprazole, a candidate for a novel antipsychotic, has an antagonistic activity against dopamine D2 receptors with a high affinity, but has a weaker potency to up-regulate D2 receptors than haloperidol in the striatum and inhibitory effects on D2-receptor binding activities and mRNA in the pituitary, when it is chronically administrated to rats. Thus the occupancy or influences in D2 receptors in the striatum are involved in the extrapyramidal side effects of typical antipsychotic drugs. These studies provide new leads to understand the pathophysiology and causes of schizophrenia and to develop more effective and safe methods of treatment.
In general, pain has been defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”, and hence pain is a subjective and emotional experience for each individual. For this reason, it is difficult to study pain in nonverbal animals. However, painful stimuli (noxious stimuli) can cause both a simple and an overt emotional behavior such as self-defense reaction and vocalization in animals. Therefore, we are able to measure these behaviors as nonverbal communication of pain. The vocalization responses is the natural nociceptive reaction of conscious animals and prelingual children. In the present overview, we described the methodology for objective assessment of guinea pig's vocalization response to arterial algogenics and its characteristics.