Effects of repeated withdrawal episodes, nicotine dose, and duration of nicotine exposure on the severity and duration of nicotine withdrawal in rats

Skjei, Karen L.; Markou, Athina

doi:10.1007/s00213-003-1414-1

Cited by 85 publications

(85 citation statements)

References 85 publications

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“…This 1-month duration is unusual compared to the 1-to 7-day effect seen in rats withdrawn from chronic amphetamine (eg Leith and Barrett, 1976;Kokkinidis and Zacharko, 1980;Kokkinidis et al, 1986;Lin et al, 1999;Paterson et al, 2000), cocaine Koob, 1991, 1992a;Baldo et al, 1999), opiates (Schulteis et al, 1994), ethanol (Schulteis et al, 1995), and nicotine (Epping-Jordan et al, 1998;Harrison et al, 2001). Further, attempts to increase the duration of the effect of amphetamine and nicotine withdrawal on reward threshold using repeated withdrawal from continuous administration of these drugs were not successful (Paterson et al, 2000;Skjei and Markou, 2003). Interestingly, when nicotine was given for a prolonged period of time (ie 28 vs 7 days via subcutaneous osmotic minipumps), rats exhibited a 14-15 day elevation in brain reward threshold during the subsequent withdrawal that was independent of the dose administered (Skjei and Markou, 2003).…”

Section: Discussionmentioning

confidence: 96%

“…Further, attempts to increase the duration of the effect of amphetamine and nicotine withdrawal on reward threshold using repeated withdrawal from continuous administration of these drugs were not successful (Paterson et al, 2000;Skjei and Markou, 2003). Interestingly, when nicotine was given for a prolonged period of time (ie 28 vs 7 days via subcutaneous osmotic minipumps), rats exhibited a 14-15 day elevation in brain reward threshold during the subsequent withdrawal that was independent of the dose administered (Skjei and Markou, 2003). Thus, it is hypothesized here that the duration of the chronic drug treatment is an important factor in determining the duration and magnitude of the brain reward deficit, and further investigation of this relation may offer new insights into the specificity of the neurobiological mechanisms underlying the enduring affective disturbances associated with long periods of drug use.…”

Section: Discussionmentioning

confidence: 99%

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Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Spielewoy

Markou

2002

Neuropsychopharmacol

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Phencyclidine (PCP) is a drug of abuse that has rewarding and dysphoric effects in humans. The complex actions of PCP, and PCP withdrawal in particular, on brain reward function remain unclear. The purpose of the present study was to characterize the effects of withdrawal from acute and chronic PCP treatment on brain reward function in rats. A brain stimulation reward procedure was used to evaluate the effects of acute PCP injection (0, 5, or 10 mg/kg) or chronic PCP treatment (0, 10, 15, or 20 mg/kg/day for 14 days delivered via subcutaneous osmotic minipumps) on brain reward function. Withdrawal from acute administration of 5 and 10 mg/kg PCP produced a decrease in brain reward function as indicated by a sustained elevation in brain reward thresholds. When administered chronically, 10, 15, or 20 mg/kg/day PCP induced a progressive dose-dependent potentiation of brain stimulation reward, while cessation of the treatment resulted in significant elevations in reward thresholds reflecting diminished reward. Specifically, withdrawal from 15 or 20 mg/ kg/day PCP induced a depression in brain reward function that lasted for the entire month of observation. These results indicate that prolonged continuous administration of high PCP doses facilitates brain stimulation reward, while withdrawal from acute high PCP doses or chronic PCP treatment results in a protracted depression of brain reward function that may be analogous to the dysphoric and anhedonic symptoms observed in PCP dependence, depression, and schizophrenia.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Spielewoy

Markou

2002

Neuropsychopharmacol

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“…The magnitude of nicotine dependence, as well as the negative state and dysphoria associated with nicotine withdrawal, are good predictors of smoking relapse (Ockene et al, 2000). Indeed, ICSS studies in rats demonstrate reduced sensitivity to rewarding stimulation (anhedonia) following spontaneous withdrawal from nicotine minipump extraction (Skjei and Markou, 2003;Kenny et al, 2003a;Yamada et al, 2010;Epping-Jordan et al, 1998;Vlachou et al, 2011). However, the persistence of anhedonia following nicotine withdrawal is not a consistent finding in the literature.…”

Section: Discussionmentioning

confidence: 99%

Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice

Hilário

Turner

Blendy

2012

Neuropsychopharmacol

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Tobacco dependence is an addiction with high rates of relapse, resulting in multiple quit attempts in individuals who are trying to stop smoking. How these multiple cycles of smoking and withdrawal contribute to nicotine dependence, long-term alterations in brain reward systems, and nicotine receptor regulation is unknown. Therefore, to evaluate how multiple exposures of nicotine and withdrawal periods modulate rewarding properties of nicotine, we used intracranial self-stimulation to measure alterations in the threshold of brain stimulation reward. In addition, we employed the conditioned place preference (CPP) paradigm to evaluate positive context conditioning following each withdrawal period and measured levels of neuronal nicotinic receptors in cortex, striatum, and hippocampus. We found that repeated nicotine exposure and withdrawal enhanced brain stimulation reward and reward sensitivity to acute injections of nicotine. This increased reward was reflected by enhanced CPP to nicotine. Chronic nicotine is known to up-regulate nAChRs (nicotinic acetylcholine receptors) and we found that this up-regulation was maintained for up to 8 days of withdrawal in the striatum and in the hippocampus, but not in the cortex, of animals exposed to multiple nicotine exposure and withdrawal periods. These results demonstrate that repeated exposures to nicotine, followed by withdrawal, induce a persistent increase in both brain reward function and sensitivity to the hedonic value of nicotine and long-lasting up-regulation of neuronal nicotinic receptors. Together, these data suggest that a continuing increase in brain reward function and enhanced sensitivity to nicotine reward following repeated withdrawal periods may be one reason why smokers relapse frequently.

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“…Withdrawal-related decreases in the brain reward system in humans has been modeled using the intracranial self stimulation (ICSS) procedure, in which rats press a lever to deliver electrical stimulation to reward-related brain areas. Nicotine withdrawal increases ICSS threshold [26,81,156]. Thus, several nicotine withdrawal symptoms reported in humans have been modeled and studied in rodents.…”

Section: Nicotinic Acetylcholine Receptors: Animal Researchmentioning

confidence: 99%

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

Portugal

Gould

2008

Behavioural Brain Research

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Tobacco smoking is a leading preventable cause of death in the United States and produces a major health and economic burden. Although the majority of smokers want to quit, few are successful. These data highlight the need for additional research into the neurobiology of tobacco dependence. Addiction to nicotine, the main psychoactive component of tobacco, is influenced by multiple factors that include individual differences in genetic makeup. Twin studies have demonstrated that genetic factors can influence vulnerability to nicotine addiction, and subsequent research has identified genes that may alter sensitivity to nicotine. In humans, genome-wide and candidate gene association studies have demonstrated that genes encoding nicotinic acetylcholine receptor (nAChR) proteins are associated with multiple smoking phenotypes. Similarly, research in mice has provided evidence that naturally occurring variability in nAChR genes is associated with changes in nicotine sensitivity. Furthermore, the use of genetic knockout mice has allowed researchers to determine the nAChR genes that mediate the effects of nicotine, whereas research with knockin mice has demonstrated that changes to nAChR genes can dramatically alter nicotine sensitivity. This review will examine the genetic factors that alter susceptibility to nicotine addiction, with an emphasis on the genes that encode nAChR proteins.

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Effects of repeated withdrawal episodes, nicotine dose, and duration of nicotine exposure on the severity and duration of nicotine withdrawal in rats

Cited by 85 publications

References 85 publications

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

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