The soul of animals is characterized by two faculties, (a) the faculty of discrimination which is the work of thought and sense, and (b) the faculty of originating local movement. Sense and mind we have now sufficiently examined. Let us next consider what it is in the soul which originates movement. Is it a single part of the soul separate either spatially or in definition? Or is it the soul as a whole? If it is a part, is that part different from those usually distinguished or already mentioned by us, or is it one of them? The problem at once presents itself, in what sense we are to speak of parts of the soul, or how many we should distinguish. For in a sense there is an infinity of parts: it is not enough to distinguish, with some thinkers, the calculative, the passionate, and the desiderative, or with others the rational and the irrational; for if we take the dividing lines followed by these thinkers we shall find parts far more distinctly separated from one another than these, namely those we have just mentioned: (1) the nutritive, which belongs both to plants and to all animals, and (2) the sensitive, which cannot easily be classed as either irrational or rational; further (3) the imaginative, which is, in its being, different from all, while it is very hard to say with which of the others it is the same or not the same, supposing we determine to posit separate parts in the soul; and lastly (4) the appetitive, which would seem to be distinct both in definition and in power from all hitherto enumerated.
It is absurd to break up the last-mentioned faculty: as these thinkers do, for wish is found in the calculative part and desire and passion in the irrational; and if the soul is tripartite appetite will be found in all three parts. Turning our attention to the present object of discussion, let us ask what that is which originates local movement of the animal.
The movement of growth and decay, being found in all living things, must be attributed to the faculty of reproduction and nutrition, which is common to all: inspiration and expiration, sleep and waking, we must consider later: these too present much difficulty: at present we must consider local movement, asking what it is that originates forward movement in the animal.
That it is not the nutritive faculty is obvious; for this kind of movement is always for an end and is accompanied either by imagination or by appetite; for no animal moves except by compulsion unless it has an impulse towards or away from an object. Further, if it were the nutritive faculty, even plants would have been capable of originating such movement and would have possessed the organs necessary to carry it out. Similarly it cannot be the sensitive faculty either; for there are many animals which have sensibility but remain fast and immovable throughout their lives.
If then Nature never makes anything without a purpose and never leaves out what is necessary (except in the case of mutilated or imperfect growths; and that here we have neither mutilation nor imperfection may be argued from the facts that such animals (a) can reproduce their species and (b) rise to completeness of nature and decay to an end), it follows that, had they been capable of originating forward movement, they would have possessed the organs necessary for that purpose. Further, neither can the calculative faculty or what is called 'mind' be the cause of such movement; for mind as speculative never thinks what is practicable, it never says anything about an object to be avoided or pursued, while this movement is always in something which is avoiding or pursuing an object. No, not even when it is aware of such an object does it at once enjoin pursuit or avoidance of it; e.g. the mind often thinks of something terrifying or pleasant without enjoining the emotion of fear. It is the heart that is moved (or in the case of a pleasant object some other part). Further, even when the mind does command and thought bids us pursue or avoid something, sometimes no movement is produced; we act in accordance with desire, as in the case of moral weakness. And, generally, we observe that the possessor of medical knowledge is not necessarily healing, which shows that something else is required to produce action in accordance with knowledge; the knowledge alone is not the cause. Lastly, appetite too is incompetent to account fully for movement; for those who successfully resist temptation have appetite and desire and yet follow mind and refuse to enact that for which they have appetite.
Part 10
These two at all events appear to be sources of movement: appetite and mind (if one may venture to regard imagination as a kind of thinking; for many men follow their imaginations contrary to knowledge, and in all animals other than man there is no thinking or calculation but only imagination).
Both of these then are capable of originating local movement, mind and appetite: (1) mind, that is, which calculates means to an end, i.e. mind practical (it differs from mind speculative in the character of its end); while (2) appetite is in every form of it relative to an end: for that which is the object of appetite is the stimulant of mind practical; and that which is last in the process of thinking is the beginning of the action. It follows that there is a justification for regarding these two as the sources of movement, i.e. appetite and practical thought; for the object of appetite starts a movement and as a result of that thought gives rise to movement, the object of appetite being it a source of stimulation. So too when imagination originates movement, it necessarily involves appetite.
That which moves therefore is a single faculty and the faculty of appetite; for if there had been two sources of movement-mind and appetite-they would have produced movement in virtue of some common character. As it is, mind is never found producing movement without appetite (for wish is a form of appetite; and when movement is produced according to calculation it is also according to wish), but appetite can originate movement contrary to calculation, for desire is a form of appetite. Now mind is always right, but appetite and imagination may be either right or wrong. That is why, though in any case it is the object of appetite which originates movement, this object may be either the real or the apparent good. To produce movement the object must be more than this: it must be good that can be brought into being by action; and only what can be otherwise than as it is can thus be brought into being. That then such a power in the soul as has been described, i.e. that called appetite, originates movement is clear. Those who distinguish parts in the soul, if they distinguish and divide in accordance with differences of power, find themselves with a very large number of parts, a nutritive, a sensitive, an intellective, a deliberative, and now an appetitive part; for these are more different from one another than the faculties of desire and passion.
Since appetites run counter to one another, which happens when a principle of reason and a desire are contrary and is possible only in beings with a sense of time (for while mind bids us hold back because of what is future, desire is influenced by what is just at hand: a pleasant object which is just at hand presents itself as both pleasant and good, without condition in either case, because of want of foresight into what is farther away in time), it follows that while that which originates movement must be specifically one, viz. the faculty of appetite as such (or rather farthest back of all the object of that faculty; for it is it that itself remaining unmoved originates the movement by being apprehended in thought or imagination), the things that originate movement are numerically many.
All movement involves three factors, (1) that which originates the movement, (2) that by means of which it originates it, and (3) that which is moved. The expression 'that which originates the movement' is ambiguous: it may mean either (a) something which itself is unmoved or (b) that which at once moves and is moved. Here that which moves without itself being moved is the realizable good, that which at once moves and is moved is the faculty of appetite (for that which is influenced by appetite so far as it is actually so influenced is set in movement, and appetite in the sense of actual appetite is a kind of movement), while that which is in motion is the animal. The instrument which appetite employs to produce movement is no longer psychical but bodily: hence the examination of it falls within the province of the functions common to body and soul. To state the matter summarily at present, that which is the instrument in the production of movement is to be found where a beginning and an end coincide as e.g. in a ball and socket joint; for there the convex and the concave sides are respectively an end and a beginning (that is why while the one remains at rest, the other is moved): they are separate in definition but not separable spatially. For everything is moved by pushing and pulling. Hence just as in the case of a wheel, so here there must be a point which remains at rest, and from that point the movement must originate.
To sum up, then, and repeat what I have said, inasmuch as an animal is capable of appetite it is capable of self-movement; it is not capable of appetite without possessing imagination; and all imagination is either (1) calculative or (2) sensitive. In the latter an animals, and not only man, partake.
Part 11
We must consider also in the case of imperfect animals, sc. those which have no sense but touch, what it is that in them originates movement. Can they have imagination or not? or desire? Clearly they have feelings of pleasure and pain, and if they have these they must have desire. But how can they have imagination? Must not we say that, as their movements are indefinite, they have imagination and desire, but indefinitely?
Sensitive imagination, as we have said, is found in all animals, deliberative imagination only in those that are calculative: for whether this or that shall be enacted is already a task requiring calculation; and there must be a single standard to measure by, for that is pursued which is greater. It follows that what acts in this way must be able to make a unity out of several images.
This is the reason why imagination is held not to involve opinion, in that it does not involve opinion based on inference, though opinion involves imagination. Hence appetite contains no deliberative element. Sometimes it overpowers wish and sets it in movement: at times wish acts thus upon appetite, like one sphere imparting its movement to another, or appetite acts thus upon appetite, i.e. in the condition of moral weakness (though by nature the higher faculty is always more authoritative and gives rise to movement). Thus three modes of movement are possible.
The faculty of knowing is never moved but remains at rest. Since the one premiss or judgement is universal and the other deals with the particular (for the first tells us that such and such a kind of man should do such and such a kind of act, and the second that this is an act of the kind meant, and I a person of the type intended), it is the latter opinion that really originates movement, not the universal; or rather it is both, but the one does so while it remains in a state more like rest, while the other partakes in movement.
Salegon
Guys that let a monkey suck their nippel are humans aswell.
Silky Johnson
Genetic differences among patients are likely to contribute to differences in their response to psychotropic medications, as well as their risk of developing adverse effects (Malhotra, Murphy, & Kennedy, 2004). The term pharmacogenetics refers to the use of molecular genetic approaches to investigate differences in drug response and tolerability. One approach to understanding pharmacogenetic differences is through the study of pharmacokinetics, which was discussed in last month's Psychopharmacology article (Howland, 2006). The other main approach is through the study of pharmacodynamics (Evans & McLeod, 2003).
PHARMACOGENETICS AND PHARMACODYNAMICS
When a drug is administered, it is absorbed and distributed to its site of action, where it interacts with its particular target(s), undergoes metabolism, and is then excreted (Brunton, Lazo, Parker, Buxton, & Blumenthal, 2006). Pharmacodynamics refers to a drug's mechanism of action at its particular target(s), which includes its therapeutic effects and any adverse effects. Psychotropic drug targets typically are various enzymes, transporters, and receptors that regulate the synthesis, transmission, and/or degradation of different chemical neurotransmitters, such as serotonin (5HT) and dopamine (DA), in the brain.
The different enzymes, transporters, and receptors found in the brain each exist as a protein that is produced by a different gene. Therefore, for each person, these proteins are genetically determined, contributing to the known inheritance of mental disorders and inherited differences in drug effects (Evans & McLeod, 2003; Malhotra et al., 2004).
Variations in the genetic code for a particular gene are referred to as "genetic polymorphisms." Multiple genetic polymorphisms have been identified for some of the neurotransmitter enzymes, transporters, and receptors of particular interest in clinical psychopharmacology. Genetic polymorphisms may result in alterations of the amount, structure, binding, or function of these proteins, which could affect how drugs operate on them. Pharmacogenetic pharmacodynamics research examines genetic polymorphisms of various drug targets to determine whether they can predict drug therapy response or drug-induced adverse effects.
RECENT STUDIES
Transporter Proteins
Transporter proteins bind neurotransmitters after they have been released from a neuron (nerve cell) and transport them (before they are degraded) back into the neuron, where the neurotransmitter can be reused or recycled. The 5HT transporter (5HTT), which regulates the reuptake of 5HT into neurons, is the principal site of action of selective serotonin reuptake inhibitor (SSRI) antidepressant agents. The 5HTT is the best-studied transporter system in the brain and one of the most extensively studied drug targets in pharmacogenetics research (Serretti, Benedetti, Zanardi, & Smeraldi, 2005).
Multiple genetic polymorphisms of the 5HTT gene have been identified. One particular polymorphism that has been intensively studied is characterized as a "short" or "long" form of the 5HTT gene. The short form is associated with decreased expression (i.e., decreased amount) of the 5HTT protein. A relatively consistent finding from many studies is that patients with depression who are carrying the short 5HTT polymorphism have a poor response to SSRI antidepressant agents such as fluvoxamine (Luvox®), fluoxetine (Prozac®), and paroxetine (Paxil®) (Malhotra et al., 2004; Serretti et al., 2004).
Other studies have also found that patients with the short form of the 5HTT gene are more likely to experience adverse effects of SSRI agents. For example, Murphy, Hollander, Rodrigues, Kremer, and Schatzberg (2004) found that the short form was associated with significantly more adverse effects among patients treated with the SSRI paroxetine than among those patients taking the non-SSRI mirtazapine (Remeron®). In addition, a preliminary study by Mundo, Walker, Gate, Macciardi, and Kennedy (2001) reported that depressed patients with bipolar disorder who had the short form of the 5HTT gene were more likely to develop hypomania or mania during treatment with antidepressant drugs than were those patients who had the long form. The 5HTT is being actively investigated in pharmacogenetics studies of other mood disorder therapies.
Synthetic Enzymes
Synthetic enzymes regulate the production of different neurotransmitters within various neurons throughout the brain. Tryptophan hydroxylase (TPH) is of particular interest because it is the major enzyme that synthesizes 5HT in the brain (Zhang, Beaulieu, Sotnikova, Gainetdinov, & Caron, 2004), and 5HT plays a key role in mood disorders. Compared to the 5HTT, genetic polymorphisms of TPH have not been as well studied in pharmacogenetics research. Recently, a polymorphism that results in a loss of function of TPH activity was found to be associated with a poor response to SSRI drugs (Zhang et al., 2005).
Other studies also found that TPH polymorphisms were associated with poor responses to SSRI drugs (Hassoun, Razi, & Malhotra, 2005; Serretti et al., 2005), although this finding was not replicated in a recent study (Serretti et al., 2004). Given the importance of 5HT regulation in the direct or indirect mechanism of action of many psychotropic drugs, more studies with TPH genetic polymorphisms are warranted.
Neurotransmitters
Neurotransmitters bind to receptors located on neurons, causing some change in the function or activity of that neuron (e.g., increasing or decreasing its firing rate, stimulating the release of other chemical neurotransmitters). Many different receptor subtypes exist in the brain, and they are classified by their primary binding neurotransmitter (e.g., 5HT or DA), according to a standard nomenclature (Brunton et al, 2006).
The family of 5HT receptors is extensive and the best studied. The most important 5HT receptor subtypes include 5HT-1A, 5HT-2A, and 5HT-2C receptors. They are considered important because they are directly or indirectly relevant to understanding the mechanism of action of some antidepressant drugs, such as mirtazapine and nefazodone (Serzone®), as well as the unique clinical effects of atypical antipsychotic drugs, such as clozapine (Clozaril®) and risperidone (Risperdal®). For example, recent studies have found that some 5 HT-2A receptor polymorphisms are associated with a poor response to SSRI antidepressant agents such as fluoxetine (Hassoun et al., 2005; Malhotra et al., 2004; Serretti et al, 2005). Other studies have found that 5HT-2A receptor polymorphisms are associated with a poor response to the atypical antipsychotic agent clozapine (Malhotra et al., 2004). Some of these 5HT receptor subtypes have also been implicated in the development of adverse effects with antidepressant and antipsychotic drugs. For example, Murphy et al. (2003) found that a 5HT-2A polymorphism was more likely to be associated with side effects due to paroxetine than to mirtazapine. Finally, 5HT-2C receptor polymorphisms have been recently investigated for their potential role in increasing the risk of weight gain during treatment with atypical antipsychotic drugs (Hassoun et al., 2005; Malhotra et al., 2004).
The family of DA receptor subtypes that have been identified includes DA-1, DA-2, DA-3, and DA-4 receptors. However, all known antipsychotic drugs bind to the DA-2 receptor subtype, and this may be most important for their antipsychotic efficacy. As a result, most pharmacogenetic studies of antipsychotic drug response have examined DA-2 receptor polymorphisms. These studies have found that certain DA-2 polymorphisms are associated with a poor response to haloperidol (Haldol®), risperidone, clozapine, and other antipsychotic agents (Hassoun et al., 2005; Malhotra et al., 2004). In addition, studies have investigated DA receptor polymorphisms and antipsychotic drug-induced adverse effects. For example, some DA-3 receptor polymorphisms have been found to be associated with an increased risk of akathisia and tardive dyskinesia (de Leon, Susce, Pan, Koch, & Wedlund, 2005; Evans & McLeod, 2003; Malhotra et al., 2004).
CLINICAL APPLICATIONS OF PHARMACOCENETICS AND PHARMACODYNAMICS
Recently, the AmpliChip CYP450 Test (Roche Diagnostics) became commercially available for clinical use in the analysis of genetic polymorphisms in drug-metabolizing enzymes (Jain, 2005). Unfortunately, there are no comparable pharmacogenetic "drug target" tests commercially available. Developing genetic tests for the 5HTT seems to have the most promise. Most pharmacogenetics and pharmacodynamics work has focused on the efficacy and tolerability of currently available antidepressant and antipsychotic drugs, but other studies are investigating drugs used in the treatment of mania, dementia, substance abuse, and attention-deficit/hyperactivity disorder (Evans & McLeod 2003; Hassoun et al., 2005; Malhotra et al., 2004; Nnadi, Goldberg, & Malhotra, 2005).
In addition, the availability of comprehensive genetic information (e.g., from the Human Genome Project) will elucidate the underlying genetic contributions to mental disorders. This information will be used to identify new drug targets, leading to the development of new pharmacogenetically engineered drug therapies. Molecular genetic methods are rapidly improving. It may be possible to collect a single blood sample from a patient, perform an analysis similar to that used in the AmpliChip Test, and test for genetic variations of genes that code for drug transporters, receptors, and other targets. This information can then be used in the rational selection of a drug therapy that is personalized for a particular patient, maximizing the therapeutic benefit and minimizing adverse reactions (Goldstein, 2003).
CONCLUSION
The field of pharmacogenetics and pharmacodynamics is rapidly expanding and progressing. Future care of patients receiving drug therapy will depend more and more on pharmacogenetic technologies to help in choosing among currently available therapies and in developing new therapies. Understandably, patients and families will have many questions about the use of pharmacogenetic testing in their treatment, including issues about confidentiality and ethics (Epstein, 2004). Nurses will have an important role in education and, therefore, need to understand these issues.
RJT
quote:
Originally posted by jennypie
. . .
I totally didn't want to talk about that either. ^5!
Akridrot
Vi sitter här i venten och spelar lite DOTA
å pushar på å smeker,
med motståndet vi leker
Rainborn
quote:
Originally posted by Akridrot
Vi sitter här i venten och spelar lite DOTA
å pushar på å smeker,
med motståndet vi leker
May your eyes be DUG out with a rusty spoon from World War II by some very big, Croatian dude in a very, very dark alley.
Silky Johnson
quote:
Originally posted by RJT
I totally didn't want to talk about that either. ^5!
Fuuuuuuuuuuuuuuuuuuck man. I've been talking about this for a week now. Soooooooooo sick of it. Almost done my paper though...almost done....
I just want to go to bed at a decent hour. :(
Xenocreator_PG_
quote:
Originally posted by Akridrot
Xeno might be random and confusing, but reading his posts can be...rewarding.
:wtf:
Xenocreator_PG_
quote:
Originally posted by evil_cookie
holy you're dumb.
spend less time on TA and more time in an English class.
NO! :stongue:
djnaeblis
quote:
Originally posted by Akridrot
Vi sitter här i venten och spelar lite DOTA
å pushar på å smeker,
med motståndet vi leker
vad fint! Jag förståd i alla fall. spela på!
Bidor
why would i discuss something i dont want to talk about? lol
