Gender- and morphine dose-linked expression of spontaneous somatic opiate withdrawal in mice.

Behavioural Brain Research. 2006-06-03; 170(1): 110-118
DOI: 10.1016/j.bbr.2006.02.009

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1. Behav Brain Res. 2006 Jun 3;170(1):110-8. Epub 2006 Mar 31.

Gender- and morphine dose-linked expression of spontaneous somatic opiate
withdrawal in mice.

Papaleo F(1), Contarino A.

Author information:
(1)Dipartimento di Farmacologia e Anestesiologia, Largo Meneghetti 2, 35131
Padova, Italy.

The opiate withdrawal syndrome powerfully motivates opiate seeking and abuse.
Development of effective medications for opiate withdrawal symptoms is thus a
primary research goal and heavily relies on improved experimental models. This
study was carried out to establish a clinically relevant paradigm to assess
somatic opiate withdrawal in mice. Female and male C57BL/6J mice were treated
with saline or increasing morphine doses (10-50mg/kg or 20-100mg/kg) during 6
consecutive days and tested for the spontaneous expression of somatic opiate
withdrawal signs 8, 32, 56 and 80 h after last drug administration. Contrary to
opioid receptor antagonist-precipitated procedures, the spontaneous opiate
withdrawal paradigm used here revealed interesting gender- and morphine
dose-linked differences. In particular, 56 h after last morphine administration
elevated global opiate withdrawal scores were still evident in female but not in
male mice treated with 20-100mg/kg. The severity of somatic opiate withdrawal
directly correlated with the prior cumulative morphine exposure. Timing of
expression of somatic opiate withdrawal signs also varied as a function of both
gender and morphine dose. For example, expression of paw tremors and wet dog
shakes was earlier in opiate-withdrawn male than in female mice. Overall, these
findings highlight the possibility to detect gender- and opiate dose-linked
differences in the expression and duration of somatic opiate withdrawal using a
clinically relevant research model. The behavioral paradigm described here may
represent a more appropriate tool to investigate the neurobiological bases of
opiate withdrawal as opposed to opioid receptor antagonist-precipitated opiate
withdrawal procedures.

DOI: 10.1016/j.bbr.2006.02.009
PMID: 16580078 [Indexed for MEDLINE]

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