![]() ![]() ![]() Intense craving for all drugs can anticipate withdrawal (i.e., with opioids, alcohol, nicotine) or often occurs after acute withdrawal when craving is driven by both environmental cues signifying the availability of the drug and internal states linked to negative emotional states and stress. Such binges can be hours or days in duration and often are followed by a withdrawal (“crash”) characterized by extreme dysphoria and inactivity. ![]() Psychostimulant addiction (cocaine and amphetamines) shows a pattern with a salient binge/intoxication stage. Marijuana addiction follows a pattern similar to opioids and tobacco, with a significant intoxication stage, but as chronic use continues, subjects begin to show a pattern of use characterized by chronic intoxication during waking hours followed by a withdrawal that includes dysphoria, irritability, and sleep disturbances. Nicotine addiction contrasts with the above patterns, with little obvious signs of the binge/intoxication stage, and has a pattern of intake characterized by highly titrated intake of the drug except during periods of sleep and negative emotional states during abstinence, including dysphoria, irritability, and intense craving. Alcohol addiction or alcoholism can follow a similar trajectory, but the pattern of oral drug taking often is characterized by binges of alcohol intake that can be daily episodes or prolonged days of heavy drinking and is characterized by a severe somatic and emotional withdrawal syndrome. A pattern develops in which the drug must be obtained to avoid the severe dysphoria and discomfort experienced during abstinence. With opioids, the classic drugs of addiction, a pattern of compulsive intravenous or smoked drug taking evolves that includes intense intoxication, the development of tolerance, escalation in intake, and profound dysphoria, physical discomfort, and somatic and emotional withdrawal signs during abstinence. The b-process is sluggish in onset, slow to build up to an asymptote, slow to decay, and shows sensitization (i.e., becomes larger with repeated exposure).ĭefined as responses to demands (usually noxious) upon the body (ĭifferent drugs produce different patterns of addiction that engage different components of the addiction cycle, depending on dose, length of use, and even cultural factors. In contrast, the b-process reflects a negative emotional state (dysphoria) that appears after the a-process has terminated. For addiction, the a-process consists of positive hedonic responses and occurs shortly after presentation of the drug and correlates closely with the stimulus intensity and quality and duration of the reinforcer and shows tolerance. Hedonic, positive affective, or negative affective emotional states, once initiated, were hypothesized to be modulated automatically by the central nervous system with mechanisms that reduce the intensity of the emotional state. Understanding the role of brain stress and antistress systems in addiction provides novel targets for treatment and prevention of addiction and insights into the organization and function of basic brain emotional circuitry.ĭefined behaviorally as a tendency toward rapid, unintended reactions to internal and external stimuli without regard for the negative consequences of these reactions.ĭefined as elements of behavior that result in perseveration in responding in the face of adverse consequences or perseveration in the face of incorrect responses in choice situations.ĭefined as any event that increases the probability of a response.ĭefined as the process by which removal of an aversive stimulus (e.g., negative emotional state of drug withdrawal) increases the probability of a response (e.g., dependence-induced drug intake). The brain stress and antistress systems may play a key role in the transition to and maintenance of drug dependence once initiated. This review explores the role of brain stress systems (corticotropin-releasing factor, norepinephrine, orexin, vasopressin, dynorphin) and brain antistress systems (neuropeptide Y, nociceptin ) in drug dependence, with emphasis on the neuropharmacological function of extrahypothalamic systems in the extended amygdala. Activation of brain stress systems is hypothesized to be key to the negative emotional state produced by dependence that drives drug seeking through negative reinforcement mechanisms. Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take drugs and has been linked to dysregulation of brain regions that mediate reward and stress.
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