Pleasure center is the general term used for the brain regions involved in pleasure. Discoveries made in the 1950s initially suggested that rodents could not stop electrically stimulating parts of their brain, mainly the nucleus accumbens, which was theorized to produce great pleasure. Further investigations revealed that the septum pellucidium and the hypothalamus can also be targets for self-stimulation. More recent research has shown that the so-called pleasure electrodes lead only a form of wanting or motivation to obtain the stimulation, rather than pleasure. The weight of evidence suggests that human pleasure reactions occur across a distributed system of brain regions, of which important nodes include subcortical regions (such as the nucleus accumbens and ventral pallidum) and cortical regions (orbitofrontal cortex and anterior cingulate cortex).
The pleasure center was discovered in the 1950s by two brain researchers named James Olds and Peter Milner who were investigating whether rats might be made uncomfortable by electrical stimulation of certain areas of their brain, particularly the limbic system. In the experiment, an electric current was given to rats if they entered a certain corner of a cage, with the hypothesis that they would stay away from that corner if the effect was uncomfortable. Instead, they came back quickly after the first stimulation and even more quickly after the second. In later experiments, they allowed the rats to press the stimulation lever themselves, to the effect that they would press it as much as seven-hundred times per hour. This region soon came to be known as the "pleasure center".
Rats in Skinner boxes with metal electrodes implanted into their nucleus accumbens will repeatedly press a lever which activates this region, and will do so in preference over food and water, eventually dying from exhaustion. In rodent physiology, scientists reason that the medial forebrain bundle is the pleasure center of rats. If a rat is given the choice between stimulating the forebrain or eating, it will choose stimulation to the point of exhaustion.
- 1972: A 24-year-old man with temporal lobe epilepsy, identified as patient "B-19". "He was permitted to wear the device for 3 hours at a time: on one occasion he stimulated his septal region 1,200 times, on another occasion 1,500 times, and on a third occasion 900 times. He protested each time the unit was taken from him, pleading to self-stimulate just a few more times... " 
- 1986: A 48-year-old woman with chronic pain. "the patient self-stimulated throughout the day, neglecting personal hygiene and family commitments."
The nucleus accumbens (NAcc), part of the limbic system, plays a role in sexual arousal and the "high" derived from certain recreational drugs. These responses are heavily modulated by dopaminergic projections from the limbic system. The NAcc is a recognized reward center, and activation of the pathway from the ventral tegmental area to the Nacc is believed to be rewarding, which is why it is sometimes referred to as the hedonic highway.
Brain interactions with the nucleus accumbens
The nucleus accumbens (NAcc) is a unique component of the brain, since it cannot elicit reward and learning responses without letting the brain inject dopamine into it or without letting the brain process the stimuli received. One model known as the triadic model of neurobiology has been used to attempt to explain what initiates motivation. The triadic model is based on three components of the brain that need to interact with each other constantly:
- the amygdala
- the nucleus accumbens
- the ventral medial prefrontal cortex
Current research shows that the NAcc creates a strong reward system, while the amygdala creates a harm avoidance system for an action and the ventral medial prefrontal cortex supervises that particular action. With these components working in unison, the brain is able to create what we know as motivation. Certain brain receptors also have the ability to alter the behavior of the pleasure center. Receptors in the NAcc have to open and close to respond to dopamine and serotonin. But there are other receptors that may open and close to other substances and these may inhibit or enhance the behavior of the NAcc. For example, group II metabotropic glutamate receptors (mGluR2 and mGluR3) may play a role in the pathology of cocaine addiction. It was observed that the mGluR2 and R3 receptors decrease the body’s need for cocaine. So while the NAcc might allow the body to become dependent, these receptors may also work with the NAcc to keep the dependency at an attenuated level.
The limbic system is closely connected to the prefrontal cortex. Some scientists contend that this connection is related to the pleasure obtained from solving problems. In a now-obsolete practice to cure severe emotional disorders, this connection was sometimes surgically severed, a procedure of psychosurgery, called a prefrontal lobotomy (a misnomer). Patients who underwent this procedure often became passive and lacked all motivation.
Medial Forebrain Bundle
Electrical stimulation of the medial forebrain bundle is believed to cause sensations of pleasure. This hypothesis is based upon intracranial self-stimulation (ICSS) studies. Animals will work for MFB ICSS, and humans report that MFB ICSS is intensely pleasurable. It is possible that the medial forebrain bundle carries some of the input from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc or Acb).
- Olds, James (1956) Pleasure centers in the brain. Scientific American. 105-116.
- Routtenberg, Aryeh (1978) The reward system of the brain. Scientific American. 154-164.
- Berridge, K.C., Kringelbach, M.L. (2008) Affective neuroscience of pleasure: Reward in humans and other animals. Psychopharmacology 199, 457-80.
- Kringelbach, M.L (2009). The pleasure center: Trust Your Animal Instincts. Oxford University Press. ISBN 978-0-19-532285-9.
- Liebowitz, Michael, R. (1983). The Chemistry of Love. Boston: Little, Brown, & Co.
- Whitters, W.L. & Jones-Whitter, P. (1980). Human Sexuality - A Biological Perspective. New York: Van Nostrand.
- "The Forgotten Era of Brain Chips"
- Heath, R.G. (December 1, 1963) Electrical self-stimulation of the brain in man. American Journal of Psychiatry 120: 571-577.
- Moan, C.E., & Heath, R.G. (1972) Septal stimulation for the initiation of heterosexual activity in a homosexual male. Journal of Behavior Therapy and Experimental Psychiatry 3: 23-30.
- The Owner's Manual for the Brain: Everyday Applications from Mind-Brain Research, 3rd ed. 2006. Austin: Bard Press. ISBN 1-885167-64-4
- Ernst, M (2009) Triadic model of the neurobiology of motivated behavior in adolescence
- Megan M Moran. Cystine/Glutamate Exchange Regulates Metabotropic Glutamate Receptor Presynaptic Inhibition of Excitatory Transmission and Vulnerability to Cocaine Seeking. Journal of Neuroscience 7/6/2005, Vol. 25 Issue 27, p6389-6393 5p; 4 graphs 02706474
- Hernandez G, Hamdani S, Rajabi H, et al. (August 2006). "Prolonged rewarding stimulation of the rat medial forebrain bundle: neurochemical and behavioral consequences". Behav. Neurosci. 120 (4): 888–904. doi:10.1037/0735-7044.120.4.888. PMID 16893295.
- Hedonia: TrygFonden Research Group
- Nucleus accumbens dopamine release during video games
- The role of the nucleus accumbens in the reward circuit. Part of "The Brain From Top to Bottom."
- Controversial 1950s pleasure and pain system studies - Synopsis of Dr Robert Heath's intracranial electrical stimulation research