Limbic system activities regulated

Most of the serotonin in the brain is in the brainstem, specifically in the raphe nuclei considerable amounts also are present in areas of the hypothalamus, the limbic system, and the pituitary gland. Current evidence indicates that serotonin is involved in the regulation of several aspects of behavior, including sleep, pain perception, depression, sexual activity, and aggressiveness. Some of the most important antidepressant agents are believed to prevent the reuptake of serotonin (see Chapter 33). Serotonin also may be involved in temperature regulation and in the hypothalamic control of the release of pituitary hormones. 

The concept of stress sensidzation , whereby early life stressors can induce an enhanced reactivity to later environmental adversities (review ed in Read et al., 2005), may also be relevant to the etiology of schizophrenia. This phenomenon, w hich results in abnormal activation of the HPA axis, is thought to involve alterations in the mesolimbic dopamine system (review ed in Laruelle, 2000) resulting in excessive release of dopamine, a hallmark of psychotic episodes (Laruelle et al., 1996). Taken together, it appears likely that prenatal developmental abnormalities in limbic stmctures that regulate the HPA axis predispose this system to sensitivity to stressors in early childhood and adolescent maturation. This predisposition may then play a key role in the precipitation of psychotic episodes, as well as the deterioration of brain function that accompanies the progression of the disease. 

Another hypothesis is that environmental chemicals gain access to the central nervous system via the olfactory and limbic pathways. The absence of a blood-brain barrier in the olfactory system could permit direct access of environmental chemicals through the nasal mucosa to the olfactory bulb. The olfactory and limbic systems are anatomically linked and participate directly and indirectly in the regulation of cognitive, endocrine, and immune functions. In this hypothesis, chemical exposure could induce lasting changes in limbic and neuronal activity and alter a broad spectrum of behavioral and physiological functions. 

Dopamine is an important neurotransmitter in the CNS in ganglia of the limbic system and of the pituitary gland. It regulates the involuntary motoric, psychic processes and neuroendocrine functions. Dopamine also figures as a transmitter in synapses of the kidneys. More than 7 subtypes of dopamine receptors are recognized (Table 1). Whereas stimulation of D1-receptors inactivates adenylyl cyclase, D4.7 receptors activate this enzyme. D3-receptor activation leads to the closure of Ca2+ channels. 

Synthesis The limbic system ultimately controls cortisone production by regulating release of corticotropin releasing hormone (CRH) from the hypothalamus via serotoninergic, dopaminergic and cholinergic neurons. CRH stimulates release of adreno-corticotrophic hormone (ACTH) from the anterior pituitary. ACTH activates adenylate cyclase in the adrenal cortex. The resulting cAMP activates protein kinase which enhances cholesterol esterase activity. Cholesterol esterase increases the amount of cholesterol available to mitochondria, where cortisone is made from cholesterol. ACTH also stimulates the conversion of cholesterol to pregnenolone, the first step in steroid synthesis. 

Serotonin (5-hydroxytryptamine, 5-HT) occurs in the intestinal wall, where it regulates motility and secretion in blood platelets, where it modulates platelet aggregation and vascular blood flow and in the CNS, where it acts as a neurotransmitter in areas of the midbrain. At least seven different receptors for serotonin have been characterized, which mediate a wide variety of different physiological effects. Depression and anxiety are thought to be the result of actions on 5-HTia receptors in the brain limbic system. Following release from neurons by a depolarizing action potential at central synapses, the activity of 5-HT is terminated by neuronal reuptake. This is performed by a synaptic membrane amine transporter protein, specific for 5-HT, which also co-transports sodium and chloride ions to repolarize the neuronal membrane. 

Different evidence suggests that the endocannabinoid system plays an important role in the regulation of emotional-like behaviour. Thus, the CBi cannabinoid receptor is widely distributed in limbic and cortical areas involved in the control of emotion. The administration of cannabinoid ligands produces emotional-like responses in different behavioural paradigms. Furthermore, cannabinoids also exert a modulatory role on the activity of the hypothalamic-pituitary adrenal axis (HPA), and these compounds modulate the release of several neurotransmitters involved in emotional behaviour, including CCK and GABA,... 

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