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At least 19 recordsLinked to original sources
PubMed1990

Animal models of drug withdrawal symptoms.

There have been few attempts to model subjective symptoms of drug withdrawal using animals as subjects. Two approaches for developing such models are reviewed. First, using drug discrimination methodology, it may be possible to train animals to detect the effects of withdrawal. This method has two difficulties: 1) the only discriminations trained to date involve precipitated withdrawal, and 2) the stimulus controlling behavior is difficult to specify. Second, withdrawal from many drugs of abuse produces the symptom of anxiety, and it seems likely that animal models of anxiety could be useful for studying drug withdrawal. This hypothesis has been explored most fully using subjects trained to detect the discriminative stimulus properties of the putative anxiogenic drug pentylenetetrazole (PTZ). Withdrawal from benzodiazepines or ethanol substitutes fully for PTZ, and withdrawal from cocaine, morphine, and nicotine substitutes partially for PTZ. Emerging data suggest that other animal models of anxiety may also be useful for detecting drug withdrawal. The final portion of this review examines a behavioral test that is very sensitive for detecting physical signs of withdrawal in animals. In subjects maintained on an operant baseline using food as a reinforcer, withdrawal from a drug of dependence frequently is associated with disruption of that operant behavior. For example, tetrahydrocannabinol and cocaine, drugs that are not traditionally seen as having significant withdrawal signs, produce disruption of operant responding when high-dose administration is terminated, and their readministration reverses this behavioral disruption. Based on the observation that withdrawal is associated with anxiogenic stimuli, we suggest a method to determine if disruption of operant behavior may be related to these stimuli.

Animals↗
PubMed1994

Drug withdrawal symptoms in children after continuous infusions of fentanyl.

The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p < 0.01), between length of infusion of fentanyl and NAST score (r = .70, p < 0.05), and between chloral hydrate dosage and NAST score (r = .62, p < 0.05). These findings suggest the need for an observation protocol and a possible weaning regimen after fentanyl is discontinued.

Critical Illness↗
PubMed1982

Alleviation of drug withdrawal symptoms by treatment with a potent mixture of natural lipids.

Acute treatment with morphine, as well as with other addictives, causes an initial decrease in brain membrane lipid microviscosity. Upon chronic exposure to the addictive drug, the original fluidity of brain membranes is restored, mostly due to an increase in the cholesterol content. Withdrawal of the drug leaves the membranes hyperviscous and the central nervous system supersensitive, as manifested in the abstinence syndrome. Based on this scheme of events, we have designed treatments of addicted mice with a special lipid mixture extracted from hen egg-yolk (Active-lipid, AL), which is a highly potent membrane fluidizer. In vivo treatment of morphine-addicted mice with AL, either by injection or as a diet supplement, reversed the brain membrane hyperviscosity and, concomitantly, markedly reduced, or even completely abolished the withdrawal symptoms precipitated by naloxone. Treatments with the fully saturated, rigidifying phospholipid dipalmitoyl-lecithin, exacerbated the withdrawal symptoms. These results could be the basis for a novel innocuous treatment which may facilitate the rehabilitation of drug and alcohol addicts.

Animals↗
PubMed2003

Effects of prenatal methamphetamine exposure on fetal growth and drug withdrawal symptoms in infants born at term.

To determine fetal growth and the incidence of withdrawal symptoms in term infants exposed to methamphetamine in utero, we retrospectively identified neonates whose mothers used methamphetamine during pregnancy and matched them to unexposed newborns. Exclusion criteria included multiple and preterm gestations. Although there were no differences in infant growth parameters between the methamphetamine-exposed and methamphetamine-unexposed neonates, methamphetamine exposure throughout gestation was associated with decreased growth relative to infants exposed only for the first two trimesters. In addition, there were significantly more small for gestational age infants in the methamphetamine group compared with the unexposed group. Methamphetamine-exposed infants whose mothers smoked had significantly decreased growth relative to infants exposed to methamphetamine alone. Withdrawal symptoms (as determined by a previously reported scoring system) requiring pharmacologic intervention were observed in 4% of methamphetamine-exposed infants. These preliminary findings indicate that methamphetamine use is associated with growth restriction in infants born at term.

Amphetamine-Related Disorders↗
PubMed2004

Neurobiological mechanisms in addictive and psychiatric disorders.

The studies reviewed indicate that brain stress system play an important role in the acquisition and maintenance of drugs of abuse that target the brain's reward centers. In doing so, they may destabilize these areas, making the perception of pleasure more elusive and difficult to attain. Withdrawal from drugs of abuse leads to the activation of brain CRF systems that may produce the anxiogenic response associated with drug withdrawal. More research, however, is needed to investigate the role of brain stress systems and neuropeptides in other drug withdrawal symptoms such as anhedonia. A better understanding of the brain systems underlying drug withdrawal may help in the development of improved pharmacotherapies that can alleviate drug withdrawal symptoms. The second part of the article indicated that there is a very high comorbidity between depression and drug dependence. The reviewed studies suggest that depressed patients initiate drug-taking behavior to self-medicate the symptoms associated with their psychiatric disorder. Chronic use of drugs of abuse, however, may exacerbate the symptoms of pre-existing mental disorders and subsequently increase drug-taking behavior. Conversely, professional treatment of pre-existing psychiatric disorders may decrease the use of illicit substances.

Anxiety↗
PubMed2004

Intra-administration associations and withdrawal symptoms: morphine-elicited morphine withdrawal.

On the basis of a conditioning analysis, some drug "withdrawal symptoms" are conditional responses elicited by stimuli paired with the drug effect. Prior demonstrations of conditional elicitation of withdrawal symptoms evaluated the role of environmental cues; however, pharmacological cues also typically signal a drug effect. Within each administration, early drug onset cues (DOCs) may become associated with the later, larger drug effect (intra-administration associations). This experiment evaluated the contribution of intra-administration associations to withdrawal symptoms. The results indicated that (a). 5 mg/kg morphine elicited behavioral and thermic withdrawal symptoms in rats previously injected on a number of occasions with 50 mg/kg morphine and that (b). DOC-elicited withdrawal symptoms are not a sensitized response to the opiate but rather an associative phenomenon.

Animals↗
PubMed2004

The effect of individual cocaine withdrawal symptoms on outcomes in cocaine users.

Preclinical and clinical studies suggest that individual drug withdrawal symptoms may have differential effects on addictive behaviors. The goals of this study were (1) to explore the dimensions of DSM-IV cocaine withdrawal symptoms and (2) to examine the association of these dimension and individual withdrawal symptoms with problems related to drug dependence in male and female cocaine users. The results of the principal components analyses of withdrawal symptoms supported a two factor model. The first one is labeled the depressive symptoms factor and included symptoms of depressed mood, psychomotor agitation, psychomotor retardation, craving for cocaine, insomnia, and vivid, unpleasant dreams. The second factor labeled the somatic symptoms factor included symptoms of increased appetite, hypersomnia, and fatigue. The depressive symptoms factor, in comparison to the somatic symptoms factor, was associated with more frequent reporting of having chemical dependency treatment, having depressed mood for longer than 2 weeks, and trading cocaine for sex. When the individual withdrawal symptoms were examined, depressed mood, psychomotor agitation, vivid, unpleasant dreams, and fatigue were associated with more frequent reporting of some of these outcomes. Our findings support two dimensions in cocaine withdrawal symptoms with differential effects on cocaine dependence outcomes.

Adult↗
PubMed1978

Withdrawal syndromes associated with antipsychotic drugs.

Withdrawal symptoms frequently follow abrupt discontinuation of antipsychotic compounds. In addition to other somatic symptoms, withdrawal-emergent dyskinesias may be observed. "Covert dyskinesia" refers to a masked form of tardive dyskinesia that becomes clinically detectable only after antipsychotic drugs are withdrawn or their dosage is reduced. Withdrawal dyskinesia appears under similar circumstances but disappears spontaneously in 6 to 12 weeks. Cholinergic overactivity and changes in dopamine-acetylcholine balance in the basal ganglia may underlie these withdrawal syndromes. The principal value of the concept of covert dyskinesia is in the secondary and tertiary prevention of tardive dyskinesia through early discovery and treatment.

Acetylcholine↗