Intracranial Self Stimulation ICSS

The intracranial self-stimulation (ICSS) procedure is used to study the effects of drugs on reward processes, or regions involved in pleasurable feelings, in the brain. In humans undergoing brain surgery, researchers were able to induce limb movements or produce sensations by electrically stimulating various regions of the cortex. Similarly, electrical stimulation of certain brain regions in the rat was reinforcing, or pleasurable, thus creating a new area for brain research. An electrode capable of delivering varying intensities and durations of electrical impulses was implanted in the brain of a rat. These animals could be trained to press a lever that would activate the implanted electrode, sending a small impulse to a specific brain region. In addition, animals could also be trained to press a lever that would ''shut off ' brain impulses in other regions. These animals will give up food and water, and even sexual activities, in order to perform tasks that lead to brain stimulation in certain regions. Based on these results, this procedure was recognized as a method by which mechanisms underlying drug addiction could be studied.

Early work in brain stimulation involved mapping out which brain areas would support self-stimulation in animals, primarily rats. Animals were trained using operant procedures in which a press of the lever would deliver an electrical stimulus to the brain. Researchers found two systems of reward in the rat brain using ICSS: a dorsal (closer to the back of the animal) system projecting from the caudate/septal area through the dorsal thalamus to the tectum, and a ventral system (closer to the abdomen of the animal), the medial forebrain bundle. The ''punishment'' system seemed to be located in the diencephalon and the tegmentum. Rats will readily self-stimulate when electrodes are implanted into the ventral tegmental area (VTA) and substantia nigra, brain regions associated with reward. Researchers hypothesized that, by stimulating these brain regions, the rats were activating their own dopamine neurons electrically, thus producing the effects of reward. Dopamine is a neurotransmitter found in the brain of rodents and primates. This neurotransmitter is thought to be involved in the rewarding or pleasurable effects of drugs of abuse.

Drugs can interact with the established pattern of self-stimulation in an animal. Interactions between drugs and ICSS suggest that these treatments act through the same mechanisms. The rate at which the animal presses the lever is correlated with the intensity of the current being delivered to the brain. However, the rate at which the animal presses the lever is not necessarily related to the amount of pleasure the animal is experiencing. The influences of various drugs on self-stimulation behavior can be due to a variety of effects, such as increases or decreases in general activity, changes in motivation or memory, etc. To state that a drug has an effect on self-stimulation, these possibilities must be ruled out. To do this, one can compare data describing the effects of the test drug in other behavioral paradigms (e.g., locomotor activity, self-administration) to the effects observed in ICSS.

Despite these limitations, researchers have collected interesting data, examining the effects of various drugs of abuse on rate of self-stimulation. Animals were trained to press a lever that would result in electrical stimulation of the brain. Then, the intensity of the stimulation was lowered so that the animals would not press the lever very often. When the animals were given the psychomotor stimulant amphetamine, the animals began to press the lever at a very high rate that gradually declined to the rate observed at low stimulation intensities. To rule out that animals might be pressing the lever more often due to the motor-activating effects of amphetamine, these researchers looked at the effects of amphetamine on lever-pressing in rats that were not receiving any brain stimulation. They saw no changes in lever-pressing before or after the rats were given amphetamine. Thus, they concluded that amphetamine enhances the reward produced by the subthreshold stimulation by activating reward pathways in the brain.

Another approach in using ICSS to measure the rewarding effects of drugs is to train animals to regulate the intensity of the stimulation that they receive in the brain. Animals are given access to two levers in the test chamber. When the animal pressed one of these levers for the first time, a relatively high level of brain stimulation was delivered. However, subsequent presses of the lever deliver decreasing levels of stimulation. The animal can "reset" the stimulation to the original high level by pressing the second lever. Under these conditions, the animals reliably reset their stimulation level once it drops below a certain point. From this measurement, researchers are able to determine each animal s reward threshold in a very reliable way. Regardless of the initial level of stimulation, these animals would press the reset lever at the same intensity of stimulation. Drugs such as amphetamine and morphine have ''threshold-lowering'' effects, such that the animals would press the reset lever at a lower intensity after receiving these drugs. This suggests that these drugs are themselves reinforcing, or pleasurable.

ICSS has been used to study the effects of the chronic administration of cocaine. Depending on the frequency of administration and amount of cocaine given, difference changes in ICSS responses have been observed. When low doses of cocaine were given once or several times a day, no changes in the ICSS threshold were observed. However, when higher doses of cocaine were administered for seven days, the reward threshold was increased in these animals, indicating that tolerance to the rewarding effect of cocaine had developed and/or that the effects of cocaine had become less pleasurable. In addition, animals that self-administered cocaine also exhibited this increase in the ICSS reward threshold. These experimental results are comparable with those observed in human drug users who take increasingly greater amounts of drug to achieve the same pleasurable effect over a long period of time.

BIBLIOGRAPHY

Greenshaw, A., & Wlshart, T. (1987). Effects of drugs on reward processes. In A. Greenshaw & C. Dourish, (Eds.), Experimental psychopharmacology: Concepts and methods. Clifton, NJ: Humana Press. Hammer, R., Egilmez, Y., & Emmett-Oglesby, M. (1997). Neural mechanisms of tolerance to the effects of cocaine. Behavioral Brain Research, 84, 225-239. Silverman, P. (1978). Animal behaviour in the laboratory. New York: Pica Press.

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