Neuropsychopharmacology Concepts: Overview and Analysis

Neuropsychopharmacology Concepts: Overview and Analysis Cole Garcia Introduction This research paper was written explore and demonstrate my personal interests in my field of study, neuropsychopharmacology. The research papers discussed were selected to provide a diverse range of topics within the field, and to convey findings that I’ve deemed to be particularly unique or useful in real-life application. Neuropsychopharmacology: a Brief, Multidimensional View Although frequently demonstrated to be neurotoxic in humans, amphetamines have been therapeutically prescribed and abused recreationally since their discovery over a century ago. One form of amphetamine, infamous for its high rates of addiction and toxicity in users, is methamphetamine (METH). The researchers of this study posed the question of whether the traditional animal models demonstrating that METH use decreases caudate-putamen dopamine levels (DA) can be applied to human patterns of abuse and resulting neurotoxicity. Substantial research has indicated that tolerance to METH reduces many of the toxic effects associated with binge use of the drug. To demonstrate this, the researchers aimed to find if the neural death in rats associated with an acute METH binge following an escalation-dose (ED) pretreatment would be less severe than the damages stereotypically observed after high dose â€Å"binge† exposure without prior ED treatment. The researchers hypothesized that curr ent research overstates the neurotoxicity associated with METH abuse, since animal model studies fail to account for the ED pattern typically observed before binge-use in most human users of METH. To test their hypothesis, the researchers selected groups of healthy male rats for experimentation. The living conditions of the rats were kept stable and relatively natural. Following a normalization period of at least a week, the rats were administered three separate, increasing doses of d-METH each day for two weeks. The period began with a dosage of 0.1mg/kg and finished with a dosage of 4.0mg/kg, a dose considered extraordinarily high for human users. Following the last day of ED pretreatment, the rats were administered a â€Å"binge† regimen, consistent with those traditionally used in similar studies, of four injections of 6mg/kg at two hour intervals. Throughout the experiment, a variety of data regarding behavioral responses to the drug, physiological responses like hyperthermia, and other immediately observable variables were gathered. Three days after the last METH administration, the rats were killed and their brains were analyzed to measure DA content and the leve ls of DAT transporter binding that is typically reduced as a result of METH binge use. Analysis of the data showed that the acute METH binge administration produced lower than average neurotoxicity in rats that were subject to ED pretreatment. All but one of the post-mortem neural tissue measurements displayed a reduction in damages in the pretreated rats while non-pretreated rats displayed normal levels of neural death following the acute binge. In vitro data showed similar results; rats administered the binge regiment without pretreatment displayed stereotypic movement associated with acute an METH binge. Most significantly, the data showed that the reduction in DA levels typically resulting from METH binge administration was considerably less severe in the rats that underwent ED pretreatment. All p values for this data were less than 0.01 or 0.001. The researchers concluded that a significant portion of the neurotoxic effects of METH binge use observed in rats can be attenuated by a prior escalation dose regimen. Since past studies on METH’s neurotoxicity fail to examine the drug’s neurotoxicity in subjects that followed â€Å"regular† human patterns prior to administration of toxic doses, the researchers argued that future research on stimulant abuse should follow an escalation dose pretreatment in order to produce data that is actually applicable to the majority of human subjects. For psychopharmacology researchers concerned with reducing drug related harm, this is extremely important information and future studies should explore further by finding a rodent ED pretreatment that is most comparable to actual human behavior patterns. The effects of hallucinogenic drugs like psilocybin and LSD have been documented to profoundly alter visual perceptions of the world. For thousands of years, psilocybin and similar substance have been used for spiritual and religious rituals in many different cultures. Until recently, the neurological causes for the visual distortions have been largely unknown. Past research has found that the serotonin receptors, 5-HT2A, 5-HT2B, 5-HT2C, are likely highly involved in visual processing as well as hallucinations associated with Schizophrenia and Parkinson’s disease. Past animal studies indicate that activation of the 5-HT2A receptors increases the excitability of the visual cortex. This research paper, published by the Journal of Neuroscience, investigates the possibility that the activation of 5-HT2A receptors through psilocybin causes modulation of parietal-occipital ÃŽ ± oscillations, resulting this noted increase in excitability of visual processors. The researchers further hypothesized that the hallucinations could be caused by the 5-HT2A receptor modulation of the visual cortex’s visual recognition â€Å"potentials.† Specifically, the researchers questioned whether or not the P1 and N170 (visual recognition and mid-level processing potentials) are modulated by psilocybin’s activations of the 5-HT2A receptors. The researchers attempted to answer these questions by administering across multiple doses a combination of psilocybin, a placebo, and ketanserin (a 5-HT2A antagonist to cancel the effects of psilocybin in certain trials) to seventeen healthy individuals on four different experimental days. After administration of each drug(s), visual stimulus and response tests were carried out with continuous EEG monitoring during each trial. ÃŽ ± waves were measured for a short duration before and after the administration of the visual stimulus, and the resulting strengths were compared. Six hours after the administration of the drugs, the subjects were required to fill out a standardized questionnaire addressing their subjective visual alterations and changes in perception as a result of the drugs administered on that day. A variety of corrections and comparisons were performed on the data to analyze it with respect to the hypotheses, and results were constructed from the implicated correlations. The first finding was that all subjects administered psilocybin subjectively experienced hallucinogenic effects or visual distortions. It was also found that the all subjects administered the placebo or ketanserin reported no hallucinations or visual distortions. P and r values for these data suggested very strong replicability and correlation. From the ÃŽ ± oscillation data, the researchers found that, under normal conditions, the ÃŽ ± oscillations were stronger during the prestimulus phase than the poststimulus phase. From the psilocybin administered subject trials, the researchers found that the ÃŽ ± oscillations were weaker than usual in the prestimulus phase and the subsequent reduction of strength was not observed in the poststimulus phase. In the placebo and ketanserin tests, no attenuation of ÃŽ ± oscillations were observed. Similarly, in trials where ketanserin was administered 1 hour following psilocybin administration, the decrease in ÃŽ ± oscillations was not observed, in dicating that the 5-HT activation following psilocybin administration is likely a cause for the observed ÃŽ ± oscillation modulation. Since ÃŽ ± oscillations have been shown to be involved in the brain’s construction of vision, the researchers concluded that the hallucinogenic effects of psilocybin are, at least partially, caused by modulation of ÃŽ ± oscillations by activation of 5-HT2A. Along with the modulation of ÃŽ ± oscillations through psilocybin’s activation of 5-HT2A, the researchers also monitored modulation of the P1 and N170 potentials. Activation of 5-HT2A was found to decrease the P1 potentials while increasing the N170 potentials during stimulus. Differences between the psilocybin and non-psilocybin trials showed trends and replicability similar to the observed ÃŽ ± oscillation data. Since these potentials have been shown to be important neurological processes associated with the brain’s recognition and construction of visual input, the researchers concluded that modulation of these important visual potentials is likely somewhat responsible for the perceived changes in visual perception. These data are among the first to show a potential neurological mechanism of action for the changes in visual perception caused by psilocybin, and future research could seek to understand how the modulation of these systems directly relates to specific vis ual changes. Alcoholism is an affliction facing millions of people worldwide and its consequences stretch far beyond the individual. Despite the mounting medical and social costs of alcohol addiction, little progress has been made towards developing effective medication as treatment. Ibogaine, a hallucinogen found in a plant native to Africa, has been anecdotally observed to reverse or undue addiction to many drugs of abuse, including alcohol. Due to its safety profile and nature of the drug’s effects, ibogaine has not yet been considered a potential medication. In this study, the researchers posed the question of whether ibogaine reduces behaviors of addiction; and, if so, how and where it produces these effects in the brain. Digging deeper, the researchers aimed to refute or confirm evidence indicating that ibogaine causes neurotoxicity at doses associated with the addiction reducing action of the drug. To answer these questions, the researchers used both behavior studies and in vivo `brain analysis. The behavior studies, testing the anti-addiction potential of ibogaine, were carried out by habituating rats to ethanol (self-administered or systematically) and then recording preferences following treatment with ibogaine. One study allowed the rats continuous access to both water and ethanol for a period of two months before administration of alcohol. In another study, rats were placed in a cage with two levers, one delivering water and the other delivering ethanol. After a period of three days without the water lever being active, ibogaine was administered and the responses were recorded. A variety of similar experiments were carried out, each of them aiming to eliminate one area of uncertainty regarding the nonspecific activities of the drug. To test for the mechanisms involved in ibogaines addiction reversal, the researchers carried out a series of ibogaine microinjections into the brains of ethanol self-administering rats. In order to clarify which area of the brain is mediates ibogaines effects, each injection was localized at a different brain structure associated with addiction and the resulting behaviors were observed. In vivo, the researchers further isolated ibogaines mechanism of action by examining the drug’s effects on cells in the rodent’s midbrain. To test for neurotoxicity, the brains of non-ibogaine treated mice were analyzed against the brains of ibogaine treated mice. After analyzing the data, the researchers found that all trials indicated attenuation of alcoholism in rats treated with ibogaine. With continuous access to alcohol before and after treatment, ibogaine treated subjects showed a reduction in preference for alcohol (when given a choice) as well as a reduction of intake when no choice was offered. Further clarifying the findings, the data showed that rats treated with ibogaine showed very little change in preference for water or sucrose control solutions. P values for these data was less than 0.02 consistently. The findings confirm that ibogaine, when administered to alcohol preferring animals, reduces the animals consumption of alcohol. Among the secondary findings, the researchers also determined the specific area mediating ibogaine’s action to be the ventral tegmental area (VTA). In trials where ibogaine micoinjections were performed in the VTA, rats decreased their consumption of alcohol considerably. In trials where the same microinjections were made in neighboring substantia nigra, no reduction in alcohol was observed. Another important result was the lack of cell death observed in mice treated with the same therapeutic doses administered to the rat subjects. This was found by observing comparing brain sections of mice exposed to known neurotoxins, ibogaine, or nothing. Similarly, no coordination impairment or bodily harm was found to occur after ibogaine administration at therapeutic doses. The researchers also found that the expression of the glial cell line-derived neurotrophic factor (GDNF) is directly affected by the drug ibogaine. This leads to what is probably the most important discovery of the data: when GDNF neutralizing antibodies are injected into the VTA of ibogaine administered alcoholic rats, the reduction of alcohol intake was negated. These findings confirm previous studies that show GDNF negate some of the effects of psychoactive drugs. The results of the experiment indicate that ibogaine is not only a potential treatment for alcoholism and addiction, but that this effect is likely carried out through increase in GDNF expression after administration of ibogaine. In the research field seeking to find treatment for drug abuse, these results are potentially revolutionary. To develop an effective treatment, future studies could seek to develop a molecule that induces the upregulation of the GDNF pathway. Alternatively, further research could be done on ibogaine in order to develop a treatment that excludes the hallucinogenic effects of the drug. Mertons theory of Anomie: Girl gangs Mertons theory of Anomie: Girl gangs Topic: Read the report A study on girls in gangs by Hong Kong Federation of Youth and evaluate the possible explanations offered by Merton’s strains towards anomie theory. After reading the report A Study on Girls in Gang by Hong Kong Federation of Youth , to a large extent I disagree to Merton’s strain towards anomie theory. Lets begin with the definition of Girls in Gang. Firstly, Girls in Gang means those girls are not contribute in any triad or serious criminal cases like murder, but they mainly committed in physical violence, stealing from shop or strangers, dishonesty to use their phone or bullying some people that they do it for fun. Secondly, they aged from 10 to 17 years old. Thirdly, gang members are or above 3 people.(Chu Yiu Kong, An Analysis of Youth Gangs in Tin Shui Wai in Hong Kong) Moreover, there are 5 types of structure in gangs. They are autonomous which is girl-dominant, auxiliary which is also girl-dominant but also rely on boy gangs, mixed which included girls and boys, independent group which is not control by anyone, satellite group which is girl-dominant, rely on boy gangs but independent. But what we know is, auxiliary and satellite are the main structures which were more common in Hong Kong society, and the decision-making are mainly from the boys. According to the theory of Structural Functionalism, the society is co-related. The social relationship extending over time and form stable patterns of interaction, then these structures in turn constituted social institutions when times gone. Therefore the social problem happens when function of an institution is not being performed properly, results from the malfunctioning. Also, from Mertons theory, deviant behavior and social disorganization were separate and distinct; tended to see each as causing the other. (Merton, 1938) In the case of Girls in Gangs, there is malfunction in the social relationship of their family, which cannot achieve prerequisite of socialization in order to inherit values, social norms, customs or ideologies by the society. That means their relationship cannot engage those girls in such a way that we find appropriate and acceptable. At the same time, their family cannot give out as the role of the family does such as give them love and belonging, financial support. Thus, girls may easily accept the deviant behaviors such as join gang to satisfy their needs. Refer to Mertons theory of strains towards anomie society, separate deviance into cultural structure and social structure. First, anomie means the low level of moral regulation which regard as normlessness, on the one hand, it is about when we are free to act and not constrained by social norms. Second, cultural structures means a hierarchy of shared values that govern our behaviors and provide us with cultural goal like achievement on education or career, material comfort of wealth. On the other hand, social structure means institutional norms which define and regulate the acceptable mode of reaching these goals.'(Merton, 1938) In other words, is to provide legitimate means by which members can pursue their goals. From his theory, there are five types of adaptations to achieve either cultural goals or social means. To a large extent, I agree to the conformity adaptations, but small extent agree to the ritualism adaptations, the innovation adaptation, the rebellion adaptations and th e retreatism adaptation did applicable to the case of girls join gangs in Hong Kong. The reasons are as of the following. The report of A study on Girls in Gangs have shown that the several reasons of the girls join gangs because of emotional attachment and protection. As most of the interviewees responded that they were lack of affiliation, which they do not have a good or even lack of relationship with their family, school or working place. In order to fulfill their mental needs or emotional attachment, they joined gangs to achieve the conformity with other people in order to lower the loneliness. Besides, girls in gangs will be named as ah-so, English means either sister-in-law or girlfriend, or ka -mui, in English means little sister, both names did not have a direct relationship, but somehow they can get protection from the gangs because of what their fake relationship is simply as same as the real family. This structure represents that the girl participating in gangs is trying to achieve their cultural goal and they do have social means which is join gangs . Thus, the girls participate in gangs d oes regard as an conformity adaptations since they have their cultural goals and social means. According to the report, A study on Girls in Gangs, the two interviewees told that they were pleasant and happy because of they can enjoy free entertainment when they join gangs. (18 years old, student) They will go to sing karaoke, dancing or go to mainland sometimes, depend on where the gangs go, and the girls in gangs do not need to pay any money, which for boys to show their gentleness and power. (16 years old, employee). From the research, it presents the girls do have cultural goal which is free entertainment regard as use the social means, but they use the same means which do not have any new goals or new means. In addition, the society was also assume the goal as materialism or material comfort, when they did not achieve their goals in legitimacy means, so they will reject the mean. Therefore, the ritualism adaptation which refers as no goals but with means cannot apply in this case. Nonetheless, the report A study on Girls in Gangs, One of the interviewees said that she joins gang because of her boyfriend is one of the members in gangs.(16, student)Furthermore, from what she has said, girls join gangs may seem to have a new goal which is find a boyfriend and maintain a stable love relationship with their partner, but it is also talk about they need emotional attachment, love and belonging by the mean. Thus, rebellion adaptation which have new goals and new means, and innovation adaptation which have goals and new means are not applicable in girls join gangs in Hong Kong, because they do not have the new goals and new means. The above report datas also presented some of the girls know that when they need to leave the gang. The report shown that girls join gangs which they think they were smart enough to protect themselves, and they know what they are doing, they always did something for aim.(18, employee) This shows that they are not as what retreatlism adaptation means have no goals and no means to do some deviant behavior, and what Merton regards as true deviant. Therefore, retreatlism adaptation cannot apply in this case, as the girls join gangs for goals. In our life, different countries or places may bring a different social structure. Compare to America, Hong Kong is rarely have serious criminal cases, and the girls in gangs which were totally different. Mertons theory can explain why rates of deviant behavior are higher in some sectors of the society than in others. American culture is characterized by great emphasis on the accumulation of wealth as a success symbol without a corresponding emphasis on using legitimate means to match toward their goal.'(Marshall B. Clinard, 1964) Refer to the theory, it told that in America society, if the one who want to achieve goals of being wealthy, they can use any means leaned success, even illegal or criminal should be accepted by the theory. Thus, American are more focus on wealth, and do not care all other things such as relationship, love, caring, academic, and they may not facing the same problems of Hong Kong girls in gangs which was lack of affiliation or facing failure. Then, compare t o the case of Hong Kong girls in gangs, mainly concerned about the emotional attachment and conformity, join gangs seek as an instruments to achieve their conformity, they may have goals but they do not have any new means. So in this way, Mertons theory may not be appropriate to apply on the girls join gangs in Hong Kong society which is more applicable on American society. Last but not least, Hong Kong girls join gangs should be regarding something they want like affiliation to achieve with means, which is Hong Kong girls join gangs were trying to gain conformity by satisfy their emotional attachment, love and belonging. So conformity adaptation of the Mertons theory is the only one can apply and suit on the girls join gangs in Hong Kong. On the other hand, girls in gang of Hong Kong society need to fulfill their need with means, but not with new goals or new means, so other adaptation of the Mertons theory may not be the best to apply in Girls in Gangs of Hong Kong society. Therefore, to a large extent I disagree to Merton’s strain towards anomie theory. Reference Readings Chu, Yiu Kong (2005)An analysis of Youth Gangs in Tin Shui Wai in Hong Kong in Hong Kong Journal of Social Sciences NO.29 Spring/Summer 2005. Clinard, Marshall B.(1995) Robert Merton: Anomie and Social Structure in Earl Eubington and Martin S. Weinberg ed. The study of Social Problems Seven Perspectives, London : Oxford University Press. Haralambos, Michael and Holborn, Martin (2000) Sociology Themes and Perspectives ,London Collins. Mok, James and Chan Shui-ching(2008) A study on Girls in Gangs, Hong Kong : Research Centre, Hong Kong Federation of Youth Group.