A non-invasive gating device for continuous drug delivery that allows control over the timing and duration of spontaneous opiate withdrawal.
Journal of Neuroscience Methods. 2004-05-01; 135(1-2): 129-135
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1. J Neurosci Methods. 2004 May 30;135(1-2):129-35.
A non-invasive gating device for continuous drug delivery that allows control
over the timing and duration of spontaneous opiate withdrawal.
Azar MR(1), Ahmed SH, Lintz R, Gutierrez T, Stinus L, Koob GF.
(1)Department of Neuropharmacology, The Scripps Research Institute, CVN-7, 10550
North Torrey Pines Road, La Jolla, CA 92037, USA.
Opiate dependence in laboratory animals is commonly induced by two methods: (1)
subcutaneous (s.c.) insertion of morphine pellets, and (2) daily injections of
increasing doses of opiates. While both of these methods reliably induce opiate
dependence, they do not allow one to discontinue, and subsequently reestablish
steady state opiate plasma levels with minimal invasive procedures. We developed
an « ON-OFF » gating device for repeatedly and non-invasively turning ON or OFF
opiate delivery by standard osmotic minipumps. The reliability of this « device »
was tested utilizing naloxone (NAL)-precipitated somatic signs of withdrawal, and
body mass index (BMI) as measures of withdrawal. Rats were implanted with osmotic
minipumps equipped with the gating device, containing heroin (2.66 mg per day).
Three days after surgery, somatic signs of withdrawal were precipitated every 48
h by NAL (0.3mg/kg), with minipumps gated ON or OFF. For BMI, spontaneous
withdrawal was repeatedly (three times) induced by turning OFF and ON the gating
devices every 48 h. Body weights were measured every 4h from 06:00 to 22:00 h
daily. Results show that NAL precipitated intense somatic signs of withdrawal
when gating devices were ON. This effect was almost abolished when gating devices
were OFF. BMI rapidly decreased after the gating devices were turned OFF with
maximum weight loss occuring 12 h post-OFF position, and gradually returning to
baseline values after gating devices were turned back ON. These results
demonstrate the validity of the « ON-OFF » gating device for non-invasively and
repeatedly inducing physical dependence to opiates over a prolonged time.
PMID: 15020097 [Indexed for MEDLINE]