By E. Shawn. Delaware Valley College. 2018.
The remaining 15% do not cross from ample order anafranil 75 mg without a prescription mood disorder general medical condition, is impaired when the corticospinal tracts are damaged one side to the other generic anafranil 25 mg with mastercard mood disorder and autism. The fibers that cross compose the lateral in the thoracic region of the spinal cord, whereas involuntary breath- corticospinal tracts, and the remaining uncrossed fibers compose ing continues. Damage to the pyramidal motor system can be de- the anterior corticospinal tracts. Because of the crossing of fibers tected clinically by the presence of Babinski’s reflex, in which stimulation of the sole of the foot causes extension (upward move- from higher motor neurons in the pyramids, the right hemisphere ment) of the great toe and fanning out of the other toes. Babinski’s re- primarily controls the musculature on the left side of the body, flex is normally present in infants because neural control is not yet whereas the left hemisphere controls the right musculature. Nervous Tissue and the © The McGraw−Hill Anatomy, Sixth Edition Coordination Central Nervous System Companies, 2001 388 Unit 5 Integration and Coordination TABLE 11. Nervous Tissue and the © The McGraw−Hill Anatomy, Sixth Edition Coordination Central Nervous System Companies, 2001 Chapter 11 Nervous Tissue and the Central Nervous System 389 FIGURE 11. The remaining descending tracts are extrapyramidal tracts that originate in the brain stem region. Electrical stimulation of the cerebral cortex, the cerebellum, and the basal nuclei indi- rectly evokes movements because of synaptic connections within extrapyramidal tracts. Neurostimulation of the reticular formation by the cerebrum or cerebellum either facilitates or inhibits the ac- tivity of lower motor neurons (depending on the area stimu- lated) (fig. The cerebellum can influence motor activity only indirectly, through the vestibular nuclei, red nucleus, and basal nuclei. These struc- tures, in turn, affect lower motor neurons via the vestibulospinal tracts, rubrospinal tracts, and reticulospinal tracts. Damage to the cerebellum disrupts the coordination of movements with spa- tial judgment. Underreaching or overreaching for an object may occur, followed by intention tremor, in which the limb moves back and forth in a pendulum-like motion. The basal nuclei, acting through synapses in the reticular formation in particular, appear normally to exert an inhibitory FIGURE 11. People with shown in red and the extrapyramidal tracts are shown in black. Nervous Tissue and the © The McGraw−Hill Anatomy, Sixth Edition Coordination Central Nervous System Companies, 2001 Developmental Exposition lateral walls thicken to form a groove called the sulcus limitans The Spinal Cord along each lateral wall of the central canal. A pair of alar plates forms dorsal to the sulcus limitans, and a pair of basal plates forms ventrally. By the ninth week, the alar plates have special- EXPLANATION ized to become the posterior horns, containing fibers of the sen- The spinal cord, like the brain, develops as the neural tube un- sory cell bodies, and the basal plates have specialized to form the dergoes differentiation and specialization. Throughout the de- anterior and lateral horns, containing motor cell bodies. Sen- velopmental process, the hollow central canal persists while the sory neurons of spinal nerves conduct impulses toward the spinal specialized white and gray matter forms (exhibit III). Changes in cord, whereas motor neurons conduct impulses away from the the neural tube become apparent during the sixth week as the spinal cord. Alar plate Sensory Sulcus cell bodies limitans Neural tube Basal Motor Derivative plate cell bodies of neural crest (c) Neural canal Sensory fibers (b) Spinal Posterior (dorsal) horn ganglion Gray matter Lateral horn Central canal Anterior (ventral) horn Motor fibers Waldrop (a) White matter Spinal (d) nerve EXHIBIT III The development of the spinal cord. Paralysis agitans, better known as Parkinson’s disease, is a disorder of the basal nuclei involving the degeneration of Knowledge Check fibers from the substantia nigra. These fibers, which use dopamine as a neurotransmitter, are required to antagonize the effects of other 39. Diagram a cross section of the spinal cord and label the fibers that use acetylcholine (ACh) as a transmitter. De- ciency of dopamine compared to ACh is believed to produce the symptoms of Parkinson’s disease, including resting tremor. Parkinson’s disease is treated with drugs that block the effects of ACh and by the administration of L-dopa, which can be converted 41. Explain why damage to the right side of the brain primarily to dopamine in the brain. Nervous Tissue and the © The McGraw−Hill Anatomy, Sixth Edition Coordination Central Nervous System Companies, 2001 Chapter 11 Nervous Tissue and the Central Nervous System 391 CLINICAL CONSIDERATIONS The clinical aspects of the central nervous system are extensive and usually complex. Numerous diseases and developmental problems directly involve the nervous system, and the nervous system is indirectly involved with most of the diseases that afflict the body because of the location and activity of sensory pain re- ceptors.
The latest NARI to be recruited in the clinic (1997) is another bicyclic anti- depressant buy 10 mg anafranil overnight delivery depression hair loss, reboxetine (Dostert purchase anafranil 75mg line depression zombie, Benedetti and Poggesi 1997). SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) An alternative strategy was to develop drugs that are selective inhibitors of 5-HT reuptake but which, because they are chemically unrelated to the TCAs, would be unlikely to share their side-effects. This direction of research was prompted by the finding, in the late 1960s, that imipramine inhibited 5-HT reuptake, as well as that of noradrenaline, and was reinforced by the evidence that the TCA, clomipramine, was a preferential 5-HT reuptake inhibitor. The first selective serotonin reuptake inhibitor, zimelidine, was tested in the clinic in 1971 but, although it proved to be an effective antidepressant, it was subsequently withdrawn because it could apparently induce the serious neurological disorder, Guillain-Barre syndrome. Nevertheless, other SSRIs quickly followed and five agents are currently available in the UK: fluvoxamine, fluoxetine, paroxetine, sertraline and citalopram (Fig. The SSRIs are all chemically unrelated but their benefits and adverse effects are broadly similar. Their efficacy in depression is not superior to that of the TCAs but their side-effects (nausea, agitation, akathisia and sexual dysfunction), although sometimes problematic, are not life-threatening. They are also considerably safer 440 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION Figure 20. All SSRIs have other clinical applications, such as in treatment of bulimia, anxiety disorders (e. Paroxetine is the most potent inhibitor of 5-HT reuptake but, in terms of distin- guishing one compound from another, their preferential selectivity for inhibition of 5-HT rather than noradrenaline reuptake is the key criterion. Citalopram is by far the most selective in vitro (1500±3000-fold) and fluoxetine, the most frequently prescribed SSRI in the UK, is the least selective of all these agents (see Stanford 1999). In fact, it is worth questioning whether fluoxetine is a true SSRI at all. The most reliable estimates of the selectivity of fluoxetine for inhibition of 5-HT, versus noradrenaline reuptake, put this at twenty-fold, with a high Ki for noradrenaline uptake of between 1 and 10 mM. However, its active metabolite, norfluoxetine, is an even more effective inhibitor of noradrenaline uptake (Ki: 0. After chronic administration, the concentration of fluoxetine in the plasma of patients is between 0. Thus, even accounting for pharmacokinetic factors, such as protein binding, the brain concentrations of fluoxetine and norfluoxetine could well be high enough to inhibit noradrenaline reuptake. Similarly, the plasma concentration of citalopram (285 nM) after chronic administra- tion of the recommended therapeutic dose is about a hundred times greater than its Ki for inhibition of 5-HT uptake (1±10 nM), and its corresponding brain concentration is DEPRESSION 441 ten-fold greater still. With a Ki for inhibition of noradrenaline uptake of 4 mM, even this drug, the most selective of all the SSRIs, could still express this inhibition in patients. It is perhaps not surprising that, even after taking into account pharmacokinetic differences between these drugs, the therapeutic doses of the SSRIs do not parallel their Ki for inhibition of 5-HT reuptake. For instance, citalopram is about a thousand times more selective than fluoxetine for inhibition of 5-HT uptake, and yet their clinically effective doses are similar. In short, not only is their selectivity for the 5-HT transporter in vitro a poor predictor of their efficacy in vivo but it has to be questioned whether any of these compounds actually work by blocking 5-HT uptake alone. Of course, it has to be borne in mind that there are functional interactions between serotonergic and noradrenergic neurons in the CNS. Indeed, intracerebral microdialysis studies in rats have confirmed that, with the exception of fluvoxamine, all SSRIs increase the concentration of extracellular noradrenaline whether they are given systemically, or by local intracranial infusion. Such an increase could result from activation of 5-HT heteroceptors on noradrenergic neurons. There is plenty of evidence that activation of 5-HT2, and possibly 5-HT3 receptors, in the terminal field increases noradrenaline release. There is also evidence that activation of presynaptic 5-HT1A, and possibly 5-HT2, receptors, increases the activity of noradrenergic neurons in the locus coeruleus. The complex interactions between serotonergic and noradrenergic neurons that could mediate SSRI-induced changes in noradrenaline release are discussed in more detail in Stanford (1999). Because the SSRIs are derived from different chemical groups, their receptor interactions vary from compound to compound but, apart from paroxetine, none of them shows any appreciable binding to muscarinic receptors, a prime objective of their development. However, compared with other SSRIs, fluoxetine binds with moderately high affinity to human 5-HT2A (Ki: 280 nM) and 5-HT2C receptors (Ki:55n ); sertraline is a relatively potent ligand for a1-adrenoceptors, a2-adrenoceptors and D1 receptors and citalopram shows appreciable binding to 5-HT1A, a1-adrenoceptors and H1 receptors (Table 20. The extent to which any of these receptor interactions affects the efficacy of these compounds is not known.
The increased permeability of the membrane leads to a lo- These generic anafranil 50mg online anxiety 9 to 5, in turn buy 25 mg anafranil with mastercard anxiety yawning symptoms, determine the amount of depolarization calized depolarization, called the generator potential. At produced in the impulse initiation region (4) of the recep- the depolarized region, sodium ions enter the cell down tor, and events in this region constitute the next important their electrochemical gradient, causing a current to flow in link in the process. Because current is flowing into the cell at one place, it must flow out of the cell in another The Initiation of Nerve Impulses place. It does this at a region of the receptor membrane (4) called the impulse initiation region (or coding region) be- Figure 4. The threshold (colored line) is a critical produce action potentials at a frequency related to the level of depolarization; membrane potential changes be- strength of the current caused by the stimulus. These cur- low this level are caused by the local excitatory currents rents, called local excitatory currents, provide the link be- and vary in proportion to them, while the membrane ac- tween the formation of the generator potential and the ex- tivity above the threshold level consists of locally pro- citation of the nerve fiber membrane. The lower trace shows a series of In complex sensory organs that contain a great many in- different stimuli applied to the receptor, and the upper dividual receptors, the generator potential may be called a trace shows the resulting electrical events in the impulse receptor potential, and it may arise from several sources initiation region. Often the receptor potential is given a No stimulus is given at A, and the membrane voltage is at special name related to the function of the receptor; for ex- the resting potential. At B, a small stimulus is applied, pro- ample, in the ear it is called the cochlear microphonic, ducing a generator potential too small to bring the impulse while an electroretinogram may be recorded from the eye. As in all ex- importance in the transduction process because it is the citable and all-or-none nerve membranes, the action poten- step in which information related to stimulus intensity and tial is immediately followed by repolarization, often to a duration is transduced. The strength (intensity) of the stim- level that transiently hyperpolarizes the membrane poten- ulus applied (in Fig. Since the brief stimulus has been removed by this time, no Varying the intensity of the stimulation will correspond- further action potentials are produced. A longer stimulus of ingly vary the generator potential, although the changes the same intensity (D) produces repetitive action potentials will not usually be directly proportional to the intensity. C, A brief, but intense, stimulus can cause a single action po- lus intensities and durations. D, Maintaining this stimulus leads to a train of action po- stimulus, the membrane is at rest. E, Increasing the stimulus intensity leads to an increase in duces a generator potential too small to cause membrane excita- the action potential firing rate. CHAPTER 4 Sensory Physiology 67 the repolarized membrane to threshold at a rate propor- tional to their strength. During this time interval, the fast Stimulus sodium channels of the membrane are being reset, and an- other action potential is triggered as soon as the membrane potential reaches threshold. As long as the stimulus is main- A tained, this process will repeat itself at a rate determined by Action the stimulus intensity. If the intensity of the stimulus is in- potentials creased (E), the local excitatory currents will be stronger and threshold will be reached more rapidly. This will result in a reduction of the time between each action potential No and, as a consequence, a higher action potential frequency. Generator adaptation This change in action potential frequency is critical in com- potential municating the intensity of the stimulus to the CNS. The discussion thus far has depicted the Action generator potential as though it does not change when a potentials constant stimulus is applied. Although this is approximately correct for a few receptors, most will show some degree of Slow adaptation. In an adapting receptor, the generator poten- adaptation tial and, consequently, the action potential frequency will Generator decline even though the stimulus is maintained. As long as the stimulus is maintained, there is a steady rate of action potential firing. Part B shows C Action slow adaptation; as the generator potential declines, the in- potentials terval between the action potentials increases correspond- ingly. Part C demonstrates rapid adaptation; the action po- tential frequency falls rapidly and then maintains a constant Rapid slow rate that does not show further adaptation.