Elizabeth Navarro
Pharmacology and The Human Brain
Pharmacology is the study of how chemical agents, both natural and synthetic affect biological systems. One area within pharmacological studies is Neuropharmacology which is the study of how drugs modify the functions of the nervous system, including the brain, spinal cord, and the nerves that communicate with all parts of the body. Neuropharmacological manipulations are used as a way of perturbing cognitive function in the brain. Such perturbations can be derived from drug use or abuse or can be induced experimentally to gain insight into brain function and increase understanding of the neural foundations of cognitive functions. This wiki will briefly discuss the effects of drugs on the brain, types of pharmacological studies used to examine the brain and cognitive functioning, and a few examples of insights gained from pharmacological studies on cognitive functions.
Drugs and Neural Activity
To understand how pharmacology can increase understanding of cognitive functions, it is important to understand how medications can alter neurochemical reactions. Neurons are excitable cells within the nervous system, with the responsibility of carrying messages through electrochemical processes. Signaling between neurons involves the release of neurotransmitter molecules, as well as the response to neurotransmitter molecules, at synapses. Many drugs interfere with or alter these processes and can thereby change cognitive functions.
Neurotransmitters are altered by drugs in a variety of ways, including increasing or decreasing their synthesis, inhibiting or enhancing their transport, modifying their storage, release, or the way they are degraded, or by mimicking their activity or blocking their action at the receptor site. Drugs that specifically activate postsynaptic receptors are THC and morphine. Another drug that activates these receptors is caffeine. Caffeine prevents a neurotransmitter called adenosine from binding to its receptor. The blocking of the adenosine receptors with caffeine leads to an increase in activity and arousal levels.
Other drugs affect synaptic transmission by altering the removal of neurotransmitters from the synapse. Drugs such as cocaine and amphetamines work by blocking the dopamine transporter that removes dopamine from the synapse. Because dopamine is blocked from leaving, dopamine levels rise in the synapse and lead to feelings of well-being and euphoria.
Forms of Pharmacological Studies
There are two main forms of pharmacological studies in humans. The first form investigates the effects of chronic drug use or abuse on cognitive processes. Drug use, such as cocaine use, leads to specific changes in neurotransmission in the brain systems that underlie cognitive functions. As an example, cocaine activates dopamine receptors which then alters the physiology of the dopamine system by increasing dopamine levels in the synapse. The dopamine system is tied to reward evaluation and pharmacological research has found that these reward pathways lie in a central region of the brain called the striatum. Studies of the effects of cocaine and other drugs have been critical in advancing our understanding of the regions of the brain and the cellular mechanisms involved in reward.
An additional form of pharmacological studies is more controlled and carried out in experimental settings. Drugs are administered acutely through injection into the blood stream or injection into specific brain areas, and effects are monitored. As an example, the effects of nicotine on cognitive functions can be studied in experimental settings. Nicotine binds to acetylcholine receptors, interacting with cognitive processes that include mood, attention, memory, and appetite as well as neurological processes that can lead to addiction. Some disadvantages to this experimental approach is that there is a lack of specificity to the drug effects and much of the brain is exposed to the drug. Sorting the effects on different brain systems can thus be difficult. A more specific approach is to inject a drug into particular brain areas of experimental animals so that agents are administered in a more controlled manner.
Pharmacology and Areas of Cognition
A number of pharmacological studies have been conducted to examine the effects of various drugs on the brain, during cognitive functions such as memory, attention, and creativity. Below are examples of just a few findings from pharmacology studies that increase out understanding of cognitive functioning in the brain.
Drugs and Memory
Many studies have explored the cognitive function of memory through the use of pharmacology. For instance, Acetylcholinesterase inhibitors (AChEIs) are chemicals that increase both the level and duration of acetylcholine neurotransmitter activity and are tied to the cognitive functions of memory. Additionally, Ispronicline (TC-1734), a brain-selective alpha4beta2 nicotine acetylcholine receptor partial agonist, has shown memory-enhancing properties in rodents. A recent study has shown that the administration of TC-1734 over 10 days enhanced attention and episodic memory compared to a placebo. These findings are contributing to the development of a treatment for cognitive decline in the elderly, including age-associated memory impairment and dementia of the Alzheimer's type [2]. The neuronal nicotinic alpha-7 receptor has also been found to play a unique role in neuronal function within the human brain, including synaptic plasticity. Specific nicotinic alpha-7 receptor agonists have been developed, (MEM 63908, MEM 3454) for Alzheimer's dementia treatment[3].
Drugs and Attention
Pharmacology studies have been used to better understand the cognitive function of attention, specifically in relation to Attention Deficit Hyperactivity Disorder (ADHD). A chemical atomoxetine has been shown to block the norepinephrine transporter, which is believed to weaken ADHD symptoms by increasing norepinephrine in the synapse [4]. Additionally, neuroimaging studies in humans have shown that that methylphenidate, which is used to treat ADHD, binds to dopamine transporters in the striatum, and the dopamine transporter gene has been implicated in ADHD pathophysiology [5].
Drugs and Creativity
Pharmacology studies have shown that ropinirole, a dopamine agonist, has positive effects on creativity [6]. Researchers hypothesize that frontal lobe dysfunction associated with PD in combination with increased dopaminergic stimulation plays a role in the increase of artistic skill. Research has also shown that the limbic system contributes to creative drive and is likely to be primarily dopaminergic [7]. Dopamine is able to induce low latent inhibition – or the ability to settle into sensations—which has been shown to be a characteristic of creative individuals with high intelligence [8].
Pharmacology and Major Depressive Disorder
There are many effective antidepressants currently available to treat Major Depressive Disorder (MDD), but the likelihood that a patient will respond successfully to a single medication is low. Many patients, therefore, may suffer for months or years through a series of long and ineffective medication trials in an effort to obtain relief of their symptoms. Recent research has focused on monitoring brain function before and during treatment of MDD so that treatment can be individualized and patients will be given medication that will most benefit them. Within this research, there has been a focus on selective serotonin re-uptake inhibitors (SSRIs) which are compounds used as antidepressants. SSRIs work by inhibiting the re-uptake of the neurotransmitter serotonin into the presynaptic cell, increasing serotonin levels in the synaptic cleft. Research has shown that structurally different SSRIs leads to differences in drug interaction risks and side effects in patients [9]. Understanding the variation among SSRI antidepressants is allowing clinicians to identify reliable determinates predicting side-effects and to identify suitable patients for a particular drug. More research in this area is being conducted and is needed to fully understand how to best treat individual patients with SSRIs.
References
- McGill University Health Centre (2009, May 20). Cocaine: Perceived As A Reward By The Brain?. ScienceDaily. Retrieved June 6, 2013.
- G. Dunbar, P.H. Boeijinga, A. Demazières, C. Cisterni, R. Kuchibhatla, K. Wesnes et al. Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers. Psychopharmacology, 191 (4) (2007), pp. 919–929
- http://www.memorypharma.com/pipe.html.
- J. Polzer, M.E. Bangs, S. Zhang, M.A. Dellva, S. Tauscher-Wisniewski, N. Acharya et al. Meta-analysis of aggression or hostility events in randomized, controlled clinical trials of atomoxetine for ADHD. Biol Psychiatry, 61 (5) (2007), pp. 713–719.
- J. Biederman, S.V. Faraone. Attention-deficit hyperactivity disorder. Lancet, 366 (9481) (2005), pp. 237–248
- R.H. Walker, R. Warwick, S.P. Cercy. Augmentation of artistic productivity in Parkinson's disease. Mov Disord, 21 (2) (2006), pp. 285–286.
- A.W. Flaherty, Z.M. Williams, S. Rauch, G.R. Cosgrove, E.N. Eskandar. Deep brain stimulation of the anterior internal capsule for treatment of medically refractory Tourette syndrome. J Neurol Neurosurg Psychiatry, 57 (Suppl. 4) (2005), p. E403.
- S.H. Carson, J.B. Peterson, D.M. Higgins. Decreased latent inhibition is associated with increased creative achievement in high-functioning individuals. J Pers Soc Psychol, 85 (3) (2003), pp. 499–506.
- Harvey, B. H. (1997). The neurobiology and pharmacology of depression. A comparative overview of serotonin selective antidepressants. South African medical journal= Suid-Afrikaanse tydskrif vir geneeskunde, 87(4 Suppl), 540.
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