Psychostimulant research is quite pertinent considering that the number of new cocaine uses has more than doubled in the last decade. Dr. Paul Czoty’s lab looks at monkey models in order to better understand the neurological mechanisms underlying cocaine abuse. In the seminar, Dr. Czoty outlined the advantages to animal models and discussed the biological and environmental factors that were shown to affect cocaine sensitivity in macaques.
The brain has two main dopamine systems, the Nigrostriatal and the Mesolimbic. These systems have a variety of functions including motor control, learning, memory, hormone secretion and retinal function. Cocaine inhibits dopamine reuptake increasing the lifespan and abundance of dopamine near the receptors. The three types of animal models are predictive, isomorphic and homologous. The numerous advantages to animal models include compliance and a lack of confounding variables. In human drug abusers, the duration of use is often unknown, other drugs such as alcohol and cigarettes may influence results, self-reports may not be accurate and the placebo effect may cause bias. With animal models, there can be repeated testing and the subjects always show up.
It is interesting to note that invasive research on apes such as gorillas and chimpanzees has been limited because of ethical concerns, since they are so closely related to humans. Macaques, such as the rhesus monkey are often used instead. Nonhuman primates are quite similar to humans, can be trained to perform complex tasks and allow for long-term drug studies. With intravenous drug self-administration, the drug to be studied serves as a reinforcer. Subcutaneous vascular access ports placed near the spine of the monkey allows for simplified IV administration. The macaques may be tethered or socially housed. Social housing allows for several variables not seen in the tethered animals.
The monkeys were first individually housed for 10 months and given a PET scan with fluroclebopride, a D2 radioligand. The monkeys were then placed in social housing with 3 others. The subcutaneous access ports allowed monkeys to self-administer cocaine by pressing a lever. The amount was monitored and monkeys were given another PET scan.
Self-administration, combined with brain imaging has given scientists insights into where the cocaine acts in the brain and any long term consequences. Learning about these changes may aid in the development of drugs designed to treat cocaine addiction. PET scans radioactively label molecules of interest with a positron, the emission signal arises within the subject and the tomographic image depicts the brain in 3D. An MRI and PET scan combined can give even clearer results. A tissue-time activity curve demonstrates the distribution volume ratio, or the ratio of binding of radioligand in the basal ganglia to the cerebellum.
Vulnerability refers to genetic or environmental factors that predispose a subject to drug abuse. Anecdotally,...