Precipitated and conditioned withdrawal in morphine-treated rats

Becker, Ginger L.; Gerak, Lisa R.; Li, Jun-Xu; Koek, Wouter

doi:10.1007/s00213-009-1773-3

Cited by 12 publications

(6 citation statements)

References 23 publications

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“…In contrast, adolescents showed body weight loss only in one of the three experiments, and only after repeated administration of the highest dose examined. Body weight loss is a prominent somatic sign of opioid withdrawal, apparent from one to at most eight days after discontinuation of repeated intermittent opioid administration, in adult rats (e.g., Langerman et al 2001; Becker et al 2010) and mice (e.g., Pappaleo and Contarino 2006). The present findings therefore suggest the possibility that adolescents are less sensitive to opioid withdrawal than adults, consistent with reports that adolescent mice show less affective withdrawal from morphine than do adults, as measured in the forced swim test (Hodgson et al 2009), and that adolescent rats show less physical withdrawal (somatic signs and body weight loss) from heroin than do adults (Doherty and Frantz 2013).…”

Section: Discussionmentioning

confidence: 99%

Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J mice: age-dependent differences in locomotor stimulation, sensitization, and body weight loss

Koek

2013

Psychopharmacology

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Rationale Given evidence for age-related differences in the effects of drugs of abuse, surprisingly few preclinical studies have explored effects of opioids in adolescents (versus adults). Objectives This study compared the motor stimulating and ataxic effects of repeatedly-administered morphine in adolescent, late-adolescent, and adult mice. Methods Mice were treated with saline or morphine (10–100 mg/kg, i.p.) once per day for 4 days, and morphine (3.2–56 mg/kg)-induced locomotion was assessed 3 days or 5 weeks later. Different mice were treated repeatedly with morphine and ataxia was measured. Results Acute administration of morphine increased locomotion more in adolescents than in adults. Repeated morphine enhanced morphine-induced locomotion, assessed 3 days later, to a similar extent in each age group (minimum effective dose: 17.8 mg/kg). This sensitization was still evident 5 weeks later when the adolescents had become adult, but was smaller and occurred at a higher dose (56 mg/kg). In animals treated repeatedly with morphine as adults, sensitization was no longer apparent 5 weeks later. Intermittent morphine was at least 10-fold less potent to produce body weight loss in adolescents than in adults. Repeated morphine did not alter morphine-induced ataxia at any age. Conclusions Compared with adults, adolescents were more sensitive to the acute locomotor stimulating effects of morphine and to its long-lasting locomotor sensitizing effects, consistent with overactivity of dopamine systems during adolescence. In contrast, adolescents were less sensitive than adults to body weight loss induced by intermittent morphine, an effect indicative of morphine withdrawal in adult rodents.

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Section: Discussionmentioning

confidence: 99%

Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J mice: age-dependent differences in locomotor stimulation, sensitization, and body weight loss

Koek

2013

Psychopharmacology

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“…Likewise, in the rodent model, both avoidance of the taste cue and the onset of aversive taste reactivity behavior predict the latency to take drug, the length of the load up period, and the speed with which rats will acquire cocaine self-administration behavior (Wheeler et al, 2008). Therefore, unlike LiCl, cues that predict drugs of abuse can lead to a conditioned aversive state involving craving and withdrawal (Becker, Gerak, Li, Koek, & France, 2010; McDonald, et al, 1997, see Grigson, 2008, for a review). The TOA, then, may be involved in the development and/or expression of this more complex process.…”

Section: Discussionmentioning

confidence: 99%

“…This is unlikely, however, because there is also a 5 min ISI in the LiCl-induced CTA paradigm. However, unlike LiCl, cues that predict drugs of abuse can lead to a conditioned aversive state involving craving and withdrawal (Becker, et al, 2010; McDonald, et al, 1997). According to Wheeler et al (2011), when an intraorally infused taste cue predicts delayed access to drug, the CS elicits aversive responses such as decreased accumbens dopamine and aversive orofacial responses.…”

Section: Discussionmentioning

confidence: 99%

Bilateral lesions of the thalamic trigeminal orosensory area dissociate natural from drug reward in contrast paradigms.

Nyland¹,

Alexander²,

Liang³

et al. 2012

Behavioral Neuroscience

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Substance abuse and addiction are associated with an apparent devaluation of, and inattention to, natural rewards. This consequence of addiction can be modeled using a reward comparison paradigm where rats avoid intake of a palatable taste cue that comes to predict access to a drug of abuse. Evidence suggests rats avoid intake following such pairings, at least in part, because the taste cue pales in comparison to the highly rewarding drug expected in the near future. In accordance, lesions of the gustatory thalamus or cortex eliminate avoidance of a taste cue when paired with either a drug of abuse or a rewarding sucrose solution, but not when paired with the aversive agent, LiCl. The present study used bilateral ibotenic acid lesions to evaluate the role of a neighboring thalamic structure, the trigeminal orosensory area (TOA), in avoidance of a gustatory cue when paired with sucrose (Experiment 1), morphine (Experiment 2), cocaine (Experiment 3), or LiCl (Experiment 4). The results show that the TOA lesion disrupts, but does not eliminate avoidance of a taste cue that predicts access to a preferred sucrose solution and leaves intact the development of a LiCl-induced conditioned taste aversion. The lesion does, however, eliminate the suppression of intake of a taste cue when paired with experimenter administered morphine or cocaine using our standard parameters. As such, this is the first manipulation found to dissociate avoidance of a taste cue when mediated by a sweet or by a drug of abuse.

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“…It should be noted that assessment of above signs is not an issue of this study and in previous studies, it has been studied by various dosages including our dosages (Becker, Gerak, Li, Koek, & France, 2010). Age can also influence the mechanism of sensitization.…”

Section: Discussionmentioning

confidence: 99%

Morphine Addiction is Tolerated Better in Socialized Male Rats

Famitafreshi¹,

Karimian²

2017

Sleep Hypn

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Drug abuse in some addicts progresses to compulsive drug seeking and taking behaviors. High-risk addictive behaviors tend to make interactions between an addict and the community more complex. Socialization is a necessary process that needs to be developed to accommodate to social life.The aim of this study was to evaluate the benefits of social interaction during addiction. Forty two (42) male Sprague-Dawley rats were randomly divided into four groups: social, isolated, socialized morphine-treated (SMT) and isolated morphine-treated (IMT). At the end of the study, neurogenesis, corticosterone, nitrite/nitrate, anhedonia with forced swim test and sucrose and salt craving were examined. Neurogenesis was reduced in IMT group compared to SMT group. SMT animals and control demonstrated better forced swim test performance compared to IMT animals. Furthermore, sucrose and salt (NaCl 3%) consumption was found to be higher in IMT animals compared to SMT animals. Corticosterone was higher in IMT rats compared to SMT rats. Nitrite/nitrate was higher in IMT rats compared to SMT rats. Socialization preserves brain functions necessary for life. Hence, socialized addicts can better tolerate addiction-induced adverse effects.

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Precipitated and conditioned withdrawal in morphine-treated rats

Cited by 12 publications

References 23 publications

Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J mice: age-dependent differences in locomotor stimulation, sensitization, and body weight loss

Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J mice: age-dependent differences in locomotor stimulation, sensitization, and body weight loss

Bilateral lesions of the thalamic trigeminal orosensory area dissociate natural from drug reward in contrast paradigms.

Morphine Addiction is Tolerated Better in Socialized Male Rats

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