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.

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.

Drugs may alter the transmission of neurotransmitters to and from synapses by directly affecting the postsynaptic receptors. Some drugs activate receptors, and others block them. Drugs that activate these postsynaptic receptors are THC and morphine. A 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 is to investigate 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 is that there is a lack of specificity to the drug effects and much of the brain is exposed to the drug, Sorting out 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.

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 and a good tolerability profile. A recent study shows 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/or dementia of the Alzheimer's type [2]. The neuronal nicotinic alpha-7 receptor has also been found within the human brain to play a unique role in neuronal function, 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

Pharmacological 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 demonstrated to be a characteristic of creative individuals with high intelligence [8].

References

1. McGill University Health Centre (2009, May 20). Cocaine: Perceived As A Reward By The Brain?. ScienceDaily. Retrieved June 6, 2013.
2. 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
3. http://www.memorypharma.com/pipe.html.
4. 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.
5. J. Biederman, S.V. Faraone. Attention-deficit hyperactivity disorder. Lancet, 366 (9481) (2005), pp. 237–248
6. R.H. Walker, R. Warwick, S.P. Cercy. Augmentation of artistic productivity in Parkinson's disease. Mov Disord, 21 (2) (2006), pp. 285–286.
7. 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.
8. 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.