Dataset Information

Episodic withdrawal promotes psychomotor sensitization to morphine.

ABSTRACT: The relative intermittency or continuity of drug delivery is a major determinant of addictive liability, and also influences the impact of drug exposure on brain function and behavior. Events that occur during the offset of drug action (ie, acute withdrawal) may have an important role in the consequences of intermittent drug exposure. We assessed whether recurrent episodes of acute withdrawal contribute to the development of psychomotor sensitization in rodents during daily morphine exposure. The acoustic startle reflex--a measure of anxiety induced by opiate withdrawal-was used to resolve and quantify discrete withdrawal episodes, and pharmacological interventions were used to manipulate withdrawal severity. Startle potentiation was observed during spontaneous withdrawal from a single morphine exposure, and individual differences in initial withdrawal severity positively predicted the subsequent development of sensitization. Manipulations that reduce or exacerbate withdrawal severity also produced parallel changes in the degree of sensitization. These results demonstrate that the episodic experience of withdrawal during daily drug exposure has a novel role in promoting the development of psychomotor sensitization--a prominent model of drug-induced neurobehavioral plasticity. Episodic withdrawal may have a pervasive role in many effects of intermittent drug exposure and contribute to the development of addiction.

SUBMITTER: Rothwell PE

PROVIDER: S-EPMC3055568 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Episodic withdrawal promotes psychomotor sensitization to morphine.

Rothwell Patrick E PE Gewirtz Jonathan C JC Thomas Mark J MJ

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20100901 13

The relative intermittency or continuity of drug delivery is a major determinant of addictive liability, and also influences the impact of drug exposure on brain function and behavior. Events that occur during the offset of drug action (ie, acute withdrawal) may have an important role in the consequences of intermittent drug exposure. We assessed whether recurrent episodes of acute withdrawal contribute to the development of psychomotor sensitization in rodents during daily morphine exposure. Th ...[more]

PMID: 20811341

Similar Datasets

Project description:Deaths related to opioid use have skyrocketed in the United States, leading to a public health epidemic. Research has shown that both biological (genes) and environmental (stress) precursors are linked to opioid use. In particular, stress during adolescence-a critical period of frontal lobe development-influences the likelihood of abusing drugs. However, little is known about the biological mechanisms through which adolescent stress leads to long-term risk of opioid use, or whether genetic background moderates this response. Male and female C57BL/6J and BALB/cJ mice were exposed to chronic variable social stress (CVSS) or control conditions throughout adolescence and then tested for morphine locomotor sensitization or morphine consumption in adulthood. To examine possible mechanisms that underlie stress-induced changes in morphine behaviors, we assessed physiological changes in response to acute stress exposure and prefrontal cortex (PFC) miRNA gene expression. Adolescent stress did not influence morphine sensitization or consumption in BALB/cJ animals, and there was limited evidence of stress effects in female C57BL/6J mice. In contrast, male C57BL/6J mice exposed to adolescent CVSS had blunted morphine sensitization compared to control animals; no differences were observed in the acute locomotor response to morphine administration or morphine consumption. Physiologically, C57BL/6J mice exposed to CVSS had an attenuated corticosterone recovery following an acute stressor and downregulation of twelve miRNA in the PFC compared to control mice. The specificity of the effects for C57BL/6J vs. BALB/cJ mice provides evidence of a gene-environment interaction influencing opioid behaviors. However, this conclusion is dampened by limited locomotor sensitization observed in BALB/cJ mice. It remains possible that results may differ to other doses of morphine or other behavioral responses. Long-term differences in stress reactivity or miRNA expression in C57BL/6J mice suggests two possible biological mechanisms to evaluate in future research.

Dataset Information

Episodic withdrawal promotes psychomotor sensitization to morphine.

Publications

Episodic withdrawal promotes psychomotor sensitization to morphine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets