Limbic Dopaminergic System

Relapses and drug taking are both heavily influenced by similar factors such as the drugs neurochemistry, the user’s history, environment, and dose of the pharmacokinetics. After a period of abstinence or non-use the drugs reinstating is more often an initiation of more than one factor, namely; re-exposure to drug, stress, cues in the environment, priming of the drug to user. In the user’s mind, neurochemical responses are commonly induced through these factors, in that they create a craving by mimicking the drug and this in turn prevents reinstatement and desire to use the drug (McGovern, Xie, Segal, Siembab, & Drake, 2006).

It is believed that certain individuals are predisposed or vulnerable to addiction based on biological, psychological and social influences. The euphoric high produced by many addictive substances is the result of overstimulation of the “pleasure center” of the brain. This is the same area that controls emotions, fear, self-control and overall feelings of wellness. The presence of these foreign chemicals creates a response that the brain will crave as soon as it fades. The brain’s chemistry works against its own health, as it rewires its decision making faculties around the primary goal of finding and taking more of the drug” (1). Many people mistakenly believe that psychological addiction is somehow less serious or real than physical addiction. The psychological aspects of addiction are much more challenging to repair and recover from than the physical addiction. Psychological addiction can last for years or even a lifetime.

Addiction is defined as a chronic brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. In my opinion, compulsive drug use is a hallmark of addiction, yet a mechanistic understanding of this process has been elusive. Drug use is initiated primarily to obtain the excitatory actions of addictive drugs on brain reward systems. The reward pathway evolved to promote activities that are essential to the survival of the human race as well as other mammals (Bailey 2004). When stimulated by drugs of abuse, addiction often occurs especially in those who are genetically or otherwise “neurochemically” vulnerable

This research paper is a compilation of information gathered during lectures and through the web on the Nervous System and the Reward Pathway. This paper examines the structure of these systems, their discovery and the effects that drugs have on influencing these systems and how addictions are formed.

Activation of CB1 receptors causes increased firing of dopaminergic neurons, leading to increased extracellular dopamine, particularly in the ventral tegmental area (VTA) and nucleus accumbens (NAc) (French, 1997). It has been hypothesised that this occurs indirectly via CB1 causing disinhibition of the GABAergic interneurons in the VTA and NAc, therefore leading to excitation of the dopamine reward system (Szabo et al. 2002). This large increase in extracellular dopamine is what is thought to cause

Opioid receptors are members of the G-protein-coupled receptors (GPCRs) family, which consists of 7 transmembrane domains linked together by 3 extracellular and 3 intracellular loops (Trescot et al., 2008). The three different classes of opioid receptors are: -opioid receptor, -opioid receptor and -opioid receptor, which are distributed throughout the central and peripheral nervous systems (Trescot et al., 2008). -opioid receptors are associated with analgesia, euphoria and physical dependence and are predominately located in the brainstem and thalamus (Trescot et al., 2008). -opioid receptors, on the other hand, are primarily found in limbic brain topography, brain stem and spinal cord, and are related to dysphoria and analgesia (Trescot et al., 2008). Although -opioid receptor mechanisms are poorly understood, it has been indicated to also have psychomimetic effects (Trescot et al., 2008).

When a human encounters a reward such as sex, money, food or approval, it triggers the release of dopamine into the bloodstream, which gives a natural high. Now if drugs were introduced into a body, the brain would create up to 10 times the normal amount of dopamine, which is why drugs create such euphoria during a high (Siddiqui 4). This alarming amount of dopamine production is far beyond what the human brain can produce, thus leading to the brain solely relying upon the drug for dopamine production. Once an individual recovers from the high, the body undergoes homeostasis which is the regulation to bring the every system in the body back to normal. However the brain has become so reliant on the drug to induce dopamine it there is a shift in priority for the individual, a shift that convinces the brain the drug is necessary for survival (Siddiqui 6). With these afflictions to the human mind, research is still ongoing for exactly what causes addiction. The University of Utah is currently the leader in genetics study towards how addiction works and has come to the conclusion that addiction is inherited. The discovery is a result of isolating key genes, receptor cells and hormones that work in specific combinations that are directly related for certain addictions. The research was conducted on lab mice by administering different drugs such as alcohol and cocaine, and then meticulously identifies those that became addicted and identified certain aspects of their

In their article, “The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans,” Courtney et al. investigates the role of opioid blockade on neural systems underlying drug craving. They tested whether blockade of opioid receptors can actually reduce the salience of the methamphetamine cues.

One of the main problems in the treatment of addiction is the high rate of relapse to drug use. Consequently, two major aims of preclinical research are to elucidate the behavioral, environmental, and neural mechanisms underlying drug relapse and to discover medications that will prevent relapses. The majority of studies on these topics involve the reinstatement model. The reinstatement model is currently used in many laboratories to investigate mechanisms underlying relapse to substance seeking. In the self-administration version, by pressing a lever, animals would get a drug infusion. Then, turning off the drugs, the animals still pressed the lever, associating it with the drugs.

Although social and cultural factors are sometimes acknowledged within the field of neuroscience as contributing to addiction “the brain reward system” is the focus of the new approach to addiction.

Addiction is like all behaviours “the business of the brain”. Addictions are compulsive physical and psychological needs from habit-forming sustenances like nicotine, alcohol, and drugs. Being occupied with or involved in such activities, leads a person who uses them again and again to become tolerant and dependent eventually experiencing withdrawal. (Molintas, 2006).

The [C]raclopride plays a role in determining the extracellular dopamine in the synapse. The theory of addiction is the idea that addictive drugs have a particular nature of releasing dopamine, while psychoactive non-addictive drugs do not. Alcohol and Cannabis have been demonstrated to lack certain qualities associated with inducing the release of dopamine in comparison to [C]cocaine. Figure 2 demonstrates an increase of dopamine levels in the ventral striatum which is produced by amphetamine and alcohol administration. In regards to [C]cocaine, there is a reduction in the radiotracer as a result of decreased expression of postsynaptic dopamine receptors. Alcohol dependent individuals demonstrated to have a decreased number of radiotracers, and cannabis detected almost no changes in the dopamine receptor availability. The article itself suggested that addiction is a complex mechanism that involves external factors such as environment, along with variation in drug reaction from person to person. It was suggested he it was unlikely that a single neurotransmitter could explain every aspect associated with addiction. The role of dopamine is concluded to have a central role in addiction to ‘stimulant drugs; which directly affect the dopamine system, but less so, in reference to mediating the addiction of other drugs – such as

Opioids are important for pleasurable experience . If we observe a hedonic spectrum, we sould see, that opioids shift it in positive direction : while sweat tastes seem sweater , bitter tastes and pain seem less aversive. Blocking of opioid-mediated signalling results in decreased pleasantness of rewards. Recent studies have shown, that there is a dissotiation between the way how µ-opioid and κ-opioid – receptor related signalls modulate the perception of pain.( µ and κ come from the name of the first discoverd ligand that attach to this receptors: µ stands for morphine and κ for ketocyclazocine ). The activation of µ-opioid receptors induces

The release of Dopamine in nucleus accumbens (NAs) via mesolimbic pathway mediate a positive reinforcing phase that is critical for the development of addiction. For this reason, one might deduce that addiction would no longer exist if a scientist were to create a way to block the dopamine-reward neural basis of addiction. However, elimination of addiction is more complex than that as it requires treatment of its the neurological, psychological, genetic, and environmental components.

Addiction can come in many forms, leading to a whole array of symptoms and consequences. Addiction can impact on a person’s wellbeing, behaviour, functioning and cognitions. We have the ability to use different kinds of methods in order to find out about questions on how addiction can form, animal studies can indicate how drugs may affect humans. There have been many major advances in sophistication and complexity of animal models of addiction showing us