Research paperBehavioral evidence linking opioid-sensitive GABAergic neurons in the ventrolateral periaqueductal gray to morphine tolerance
Section snippets
Subjects
Male, Sprague–Dawley rats (300–500 g; Animal Technologies Inc., Fremont, CA, USA) were anesthetized with sodium pentobarbital (60 mg/kg, i.p.) and implanted with a guide cannula (23-gauge×12 mm long) aimed at the right ventrolateral PAG (anterior+1.0 mm; lateral+0.6 mm, ventral−4.9 mm from lambda). The guide cannula was held in place with dental acrylic affixed to two screws in the skull. A 10-mm stylet was inserted into the guide, and the rat was allowed to recover for 1 week prior to testing.
Microinjections
Experiment 1: bicuculline microinjections
Forty-three rats had injection sites located in the ventrolateral PAG (Fig. 1). Of these, 22 were pretreated with bicuculline and 21 with saline. These groups were similar prior to testing with bicuculline as indicated by the effect of the morphine screening test. Table 1 shows that microinjection of morphine into the ventrolateral PAG produced an increase in hot-plate latency and a decrease in open-field activity in both groups. Both the bicuculline and saline groups were injected with
Discussion
The present data show no evidence of tolerance to the antinociceptive effect of microinjecting the GABA antagonist bicuculline or the excitatory amino acid kainate into the ventrolateral PAG. Microinjection of bicuculline and kainate produced antinociception on trial 5 that was comparable to the antinociception produced on trial 1 and that produced in saline-pretreated controls receiving these drugs for the first time. This finding is in direct contrast to the tolerance that develops with
Acknowledgements
This investigation was supported in part by funds provided for medical and biological research by the State of Washington Initiative Measure No. 171 and by National Institute on Drug Abuse grant DA12506.
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