Central striatum

Neuropeptide Y. Neuropeptide Y [82785 5-3] (NPY) (255) is a 36-amiao acid peptide that is a member of a peptide family including peptide YY (PYY) [81858-94-8, 106338-42-5] (256) and pancreatic polypeptide (PPY) [59763-91-6] (257). In the periphery, NPY is present in most sympathetic nerve fibers, particulady around blood vessels and also in noradrenergic perivascular and selected parasympathetic nerves (66). Neurons containing NPY-like immunoreactivity ate abundant in the central nervous system, particulady in limbic stmctures. Coexistence with somatostatin and NADPH-diaphorase, an enzyme associated with NO synthesis, is common in the cortex and striatum. 

The nigrostriatal tract is one of the four main dopaminergic pathways in the central nervous system. About 75% of the dopamine in the brain occurs in the nigrostriatal pathway with its cell bodies in the substantia nigra, whose axons project in the corpus striatum. Degeneration of the dopaminergic neurons in the nigrostriatal system results in Parkinsons disease. 

High amounts of somatostatin are found in the CNS, the peripheral nervous system, the gut and the endocrine pancreas whereas the kidneys, adrenals, thyroid, submandibular glands, prostate and placenta produce rather low amounts. In particular, the hypothalamus, all limbic structures, the deeper layers of the cerebral cortex, the striatum, the periaqueductal central grey and all levels of the major sensoty pathway are brain areas that are especially rich in somatostatin. Eighty percent of the somatostatin immunoreactivity in the hypothalamus is found in cells of the anterior periventricular nucleus (Fig. 1, [1]). The gut 5 cells of the mucosa and neurons, which are intrinsic to the submucous and... 

Approaches (1) and (2) depend on sufficient cholinergic function remaining to make its supplementation feasible, while all three methods suffer from the fact that not only does ACh have other central effects (e.g. in striatum), but also numerous peripheral parasympathomimetic ones, such as increased bronchial and gastric secretion or reduced heart rate. 

Both nicotinic and muscarinic receptors are widespread in the CNS. Muscarinic receptors with a high affinity for pirenzepine (PZ), M, receptors, predominate in the hippocampus and cerebral cortex, whereas M2 receptors predominate in the cerebellum and brainstem, and M4 receptors are most abundant in the striatum. Central muscarinic and nicotinic receptors are targets of intense pharmacological interest for their potential roles in regulating abnormal neurological signaling in Alzheimer s disease, Parkinson s disease and certain seizure disorders. Nicotinic receptors are largely localized at prejunctional sites and control the release of neurotransmitters [10,11],... 

Mu and kappa receptor agonists have been shown to affect central dopaminergic activity in rodents in vivo and in vitro [78, 79]. This has been investigated with RP 60180 (51), which decreases dopamine (DA) utilization in rat prefrontal cortex and in the striatum (by 30—35 % and 10 % respectively at 1-2.5 mg/kg s.c.) whereas the mu agonist morphine causes a significant increase (90-150% and 30 40% respectively at 5 mg/kg), an effect which is abolished by RP 60180 (1 2.5 mg/kg) [80]. 

Symptomatic treatment in parkinsonism for the purpose of restoring a dopaminergic-cholinergic balance in the corpus striatum. Antiparkinsonian agents, such as benzatropine (p. 188), readily penetrate the blood-brain barrier. At centrally equi-effective dosage, their peripheral effects are less marked than are those of atropine. 

Despite the documented efficacy and safety of the psychostimulants, their mechanism of action is not fully understood. Stimulants affect central nervous system (CNS) dopamine (DA) and norepinephrine (NE) pathways crucial in frontal lobe function. The stimulants act by causing release of catecholamines from the DA axons and blocking their reuptake. Methylphenidate releases catecholamines from long-term stores, so its effects can be blocked by pretreatment with reserpine. Amphetamines, on the other hand, release catecholamines from recently formed storage granules near the surface of the presynaptic neuron, so their action is not blocked by reserpine. In addition, the stimulants bind to the DA transporter in striatum (see Figures 2.6 and 2.7) and block the reuptake of both DA and NE. This action reduces the rate that catecholamines are removed from the synapse back into the axon and leads... 

Somatostatin is a 14-amino acid peptide that induces arousal and behavioral stereotypes resembling OCD [Pitman 1989). Somatostatin is synthesized in disparate regions, including the paraventricular nucleus of the hypothalamus, the cerebral cortex, striatum, and hippocampus. When administered centrally, somatostatin delays extinction of avoidant behaviors [Vecsei and Widerlov 1988). Altemus and colleagues [1993) determined CSF somato-... 

---