Sunday, November 1, 2020 APA STYLE

Neurobiology : Cocaine and Brain Function

I chose this topic because I want to know how this harmful drug affects and changes brain patterns, also because it is so addictive. Since most of the young people get it so easy and I see with detriment how society is affected by it.

Volkow, N. D., Wang, G.-J., Telang, F., Fowler, J. S., Logan, J., Childress, A.-R., … Wong, C. (2006). Cocaine Cues and Dopamine in Dorsal Striatum: Mechanism of Craving in Cocaine Addiction. Journal of Neuroscience. https://doi.org/10.1523/JNEUROSCI.1544-06.2006

Exposure to various types of stress can elevate craving for cocaine and hasten relapse among substance dependent individuals. This investigation evaluated the effects of social exclusion on brain activity in cocaine dependent individuals.

Forty five individuals were recruited from the community (20 nontreatment seeking crack-cocaine users and 25 healthy non-drug using controls; right handed). Imaging data from two of the cocaine users were not viable due to artifacts; bringing the final sample to 43 participants (18 cocaine users and 25 controls). Control subjects did not have a history of substance abuse dependence other than nicotine and were chosen to match the Cocaine User population on the basis of gender and race. 

Forty five individuals were recruited from the community (20 nontreatment seeking crack-cocaine users and 25 healthy non-drug using controls; right handed). Imaging data from two of the cocaine users were not viable due to artifacts; bringing the final sample to 43 participants (18 cocaine users and 25 controls).

All participants met criteria for cocaine dependence and crack-cocaine was the preferred method of use. Six of the cocaine users reported marijuana use in the past month (average ± SD = 5.4 ± 1.8 days/ month). One participant reported past use of MDMA. Two participants reported past use of heroin. No participants reported past use of LSD, methamphetamine, or benzodiazepines. On the scanning day, all cocaine users had positive urine drug screens for cocaine, and four had a positive screen for marijuana. The other measured substances (e.g. opiates, amphetamines, methamphetamine, barbiturates, benzodiazepines) were all negative. All members of the control group had negative urine drug screens for all substances.

As an exploratory analysis we evaluated the relationship between gender and the brain response to social exclusion versus inclusion in the controls and cocaine users. The global mean signal change was extracted for each individual via whole brain voxel-wise calculation from within subject contrast maps of Exclusion and for Inclusion. The average and standard deviations of these global signal values were then compiled for all individuals in each of the four groups 

Effects of social exclusion relative to inclusion in cocaine users relative to controls. In this between group analysis, the brain response to social exclusion was compared to inclusion. Rest was incorporated into the model. A direct comparison of cocaine users relative to controls during social exclusion versus inclusion revealed that cocaine users had more activity in 3 clusters .

Volkow, N. D., Fowler, J. S., Wolf, A. P., Hitzemann, R., Dewey, S., Bendriem, B., ... & Hoff, A. (1991). Changes in brain glucose metabolism in cocaine dependence and withdrawal. American Journal of Psychiatry, 148(5), 621-626.

Drugs of abuse increase dopamine (DA) in the nucleus accumbens (NAc), which is an effect that is believed to underlie their reinforcing effects (Di Chiara and Imperato, 1988; Koob and Bloom, 1988). However, this acute effect does not explain the intense desire for the drug and the compulsive use that occurs when addicted subjects are exposed to drug cues such as places where they have taken the drug ,people with whom previous drug use occurred, and paraphernalia used to administer the drug. Cue-elicited craving is critical in the cycle of relapse in addiction (O’Brien et al., 1998). However, after more than a decade of imaging studies in cue-elicited craving, its underlying brain neurochemistry is still unknown (Childress et al., 2002).

This provides evidence that dopamine in the dorsal striatum (region implicated in habit learning and in action initiation) is involved with craving and is a fundamental component of addiction. Because craving is a key contributor to relapse, strategies aimed at inhibiting dopamine increases from conditioned responses are likely to be therapeutically beneficial in cocaine addiction.

Eighteen active cocaine-addicted subjects who responded to an advertisement were studied. Subjects fulfilled DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for cocaine dependence and were active users for at least the previous 6 months (free-base or crack, at least “four grams” a week). Exclusion criteria included current or past psychiatric disease other than cocaine dependence; past or present history of neurological, cardiovascular, or endocrinological disease; history of head trauma with loss of consciousness 30 min; and current medical illness and drug dependence other than cocaine or nicotine.

Dopamine in dorsal striatum and craving

In this study, we show an association between cocaine craving and DA increases in dorsal striatum (caudate and putamen). Because the main projection from DA cells to dorsal striatum arises from the substantia nigra (Haber and Fudge, 1997), this implicates the DA nigrostriatal pathway in the subjective experience of craving. This is consistent with previous imaging studies showing that activation of the putamen in cocaine abusers was associated with craving induced by intravenous cocaine as assessed by blood oxygenation level-dependent (BOLD) changes with functional magnetic resonance imaging (fMRI) [negative association (Breiter et al., 1997) as well as positive association (Risinger et al., 2005)] or by intravenous methylphenidate administration

Behavioral scales. To assess cocaine craving, we used a brief version of the Cocaine Craving Questionnaire (CCQ) (Tiffany et al., 1993), which evaluates current cocaine craving (desire to use, intention and planning to use, anticipation of positive outcome, anticipation of relief from withdrawal or distressing symptoms, and lack of control over drug use) on a seven-point visual analog scale. The average score was used as measure of cocaine craving.

PET scan. We used a high resolution tomograph (resolution 4.5 4.5 4.5 mm full-width half-maximum, 63 slices) with [11C]raclopride using methods described previously (Volkow et al., 1993).

Volkow, N. D., & Morales, M. (2015). The brain on drugs: from reward to addiction. Cell, 162(4), 712-725.

Advances in neuroscience identified addiction as a chronic brain disease with strong genetic, neurodevelopmental, and sociocultural components. We here discuss the circuit- and cell-level mechanisms of this condition and its co-option of pathways regulating reward, self-control, and affect. Drugs of abuse exert their initial reinforcing effects by triggering supraphysiologic surges of dopamine in the nucleus accumbens that activate the direct striatal pathway via D1 receptors and inhibit the indirect striato-cortical pathway via D2 receptors.

Current evidence shows that most drugs of abuse exert their initial reinforcing effects by activating reward circuits in the brain and that, while initial drug experimentation is largely a voluntary behavior, continued drug use impairs brain function by interfering with the capacity to exert self-control over drug-taking behaviors and rendering the brain more sensitive to stress and negative moods. Indeed, individuals with genetic vulnerabilities, exposed to chronic stress, or suffering from comorbid psychiatric conditions, as well as those who abused drugs during early adolescence, are at greater risk of transitioning into the automatic and compulsive behaviors that characterize addiction.

Future studies will be able to assess their contribution to the dysphoria and enhanced stress reactivity in addiction.

We recently showed abundant glutamatergic projections from the DR to VTA DA neurons that innervate the NAc, whose activation induced DA release in NAc and evoked reward (Qi et al., 2014). The DR is best known as a serotonergic structure that regulates emotional behaviors. However, findings on the role of DR serotonergic neurons in reward have been inconsistent (Cohen et al., 2015; Fonseca et al., 2015; Liu et al., 2014; McDevitt et al., 2014; Miyazaki et al., 2014), which is likely to reflect, in part, the functional diversity of these neurons. In this regard, cellular recordings from DR serotonergic neurons in behaving mice have revealed that they convey reward information through tonic as well as phasic firing and that they signal reward and punishment on multiple timescales.

The brain imaging studies in humans have documented that fast DA increases triggered by drugs are associated with the ‘‘high’’ associated with drug abuses, whereas stable DA increases are not (Volkow et al., 2008). Specifically, when large DA increases triggered by stimulant drugs were achieved over a short time period (<10 min), they were associated with reward, whereas DA increases achieved over 60 min were not. The rate dependency for a drug’s rewarding effects might explain why the time course of the subjective ‘‘high’’ is much shorter than the longer-lasting DA increases triggered by drugs such as cocaine and more notable methylphenidate

Horseman, C., & Meyer, A. (2019). Neurobiology of Addiction. Clinical obstetrics and gynecology, 62(1), 118-127.

Drugs of abuse can cause changes in the brain leading to addiction. Current scientific focus has been on how these drugs interact with the brain and the changes they cause, how those changes affect human behavior and how they may last beyond termination of drug use. Compulsiveness in seeking the drug, impulsiveness in consuming the drug, and negative affect when the drug is withheld are characteristic of addiction. Each of these characteristics has a root in neurobiology and understanding their mechanisms helps us to understand addiction and see potential targets for treatment.

Toxic addiction is defined as the physical or psychophysiological dependence on a special chemical substance, whose suppression arouses deprivation symptoms in the person. The study of addiction to different drugs gives us a new approach for knowing the strengthening systems. Because even thought we do not know precisely the nervous mechanism of these substances that cause pleasure, we suppose that they are in the same place as rewarding and strengthening the behaviour mechanisms. 

In this way the dopamine hypothesis has been developed: in this hypothesis drug addiction is closely connected with a genetic upset of this neurotransmitter, so there is a defect in the reward system. This in turn stimulates the substance abuse that increases the brain s dopamine levels.

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Gipson, C. D., Kupchik, Y. M., Shen, H., Reissner, K. J., Thomas, C. A., & Kalivas, P. W. (2013). Relapse induced by cues predicting cocaine depends on rapid, transient synaptic potentiation. Neuron, 77(5), 867-872.

Cocaine addiction is characterized by long-lasting vulnerability to relapse arising because neutral environmental stimuli become associated with drug use and then act as cues that induce relapse. It is not known how cues elicit cocaine seeking, and why cocaine seeking is more difficult to regulate than seeking a natural reward. We found that cocaine associated cues initiate cocaine seeking by inducing a rapid, transient increase in dendritic spine size and synaptic strength in the nucleus accumbens. These changes required neural activity in the prefrontal cortex.

Show evidence of long-term potentiation (LTP), including increased dendrite spine head diameter, elevated AMPA glutamate receptor-mediated synaptic currents, and AMPA receptor surface expression (Boudreau et al., 2007; Conrad et al., 2008; Kourrich and Thomas, 2009; Moussawi et al., 2009; Shen et al., 2009; Wolf and Ferrario, 2010).

Whole-cell patch recordings revealed parallel evidence for rapid synaptic potentiation during cue-induced reinstatement (Figures 3A and 3B). Withdrawal from self-administered cocaine increased A/N compared to yoked-saline rats. The A/N was further increased 15 min after initiating cue-induced reinstatement and returned to prereinstatement levels after 120 min. In contrast with the decrease in the A/N remained elevated at T = 45.

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Cocaine is a stimulant that is derived initially from a coca plant. It is a psychoactive and an addictive drug that is known to modern science. It has been seen that cocaine is a dangerous drug. However, some pleasurable aspects can be obtained from the use of cocaine, but its use is harmful to a human mind and body.

Moreover, depending on the manner with which the drug is taken, it can cause adverse effects such as erratic behaviour, paranoia, convulsions, and heart failures. Long term cocaine effects include seizures, heart attacks, memory loss, and reduced learning capacity.

Males and females consume cousin in the ratio of 3 are to 8 in Europe. As the 2014 report outlined, many cities are punctuated with excessive use of this drug with London on the lead. Similarly, in the United States of America, coke ranks second among the most used illegal drugs after cannabis("Cocaine", 2019). The largest global consumer of the drug is united states of America where it is commonly referred to as the wealthy man's drug since it is administered by either the middle class or the rich in the country. Among students, cocaine is a drug that is used in parties with the number of student users increasing over time. In addition to cocaine's use by youths, it is also common in discos and recreational centres.

Why do young people use cocaine knowing that they are damaging to the brain?