Intracranial Self-Stimulation

Intracranial self-stimulation (ICSS) is an operant behavioral paradigm in which experimental animals learn to deliver brief electrical pulses into specific regions of their own brains that are considered to be part of the brain’s reward pathways mediating both natural and ICSS reward. Several brain sites support ICSS, with the lateral hypothalamus, medial forebrain (MFB) bundle, and ventral tegmental area (VTA) among the sites that produce the most vigorous ICSS responding. Various ICSS procedures have been designed and used during the last decades since the discovery of ICSS. Two of the most commonly used ICSS procedures, which have been experimentally validated and have shown to be reward-selective, are the rate-frequency curve-shift procedure and the discrete-trial current-intensity threshold procedure. In all ICSS procedures, lowering of ICSS thresholds indicates a facilitation of brain stimulation reward, whereas elevations in ICSS thresholds reflect the diminished reward value of the stimulation and thus an anhedonic state. Acute administration of most drugs of abuse, including cocaine, amphetamine, nicotine, morphine, and heroin, lower ICSS thresholds in experimental animals. By contrast, withdrawal from chronic administration of these compounds induces elevations in ICSS thresholds, indicating an anhedonic state that resembles the negative affective state of the drug withdrawal syndrome experienced by humans. However, certain drugs of abuse, such as ethanol and cannabinoids, have shown inconsistent effects in ICSS procedures, primarily because of the minimal effects induced by these drugs in the ICSS procedure. In summary, the ICSS procedure provides unique ways to investigate the anatomical basis of reward and motivation and is an important tool for the assessment of the reward-facilitating and anhe�donic effects of various drugs of abuse with addictive properties.