PubMed · 8701124
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J C Devoghel. 1996. [Morphine].. https://pubmed.ncbi.nlm.nih.gov/8701124/
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Motor activity elicited pharmacologically from the nucleus accumbens by the mu-opioid receptor agonist D-Ala-Tyr-Gly-NMePhe-Gly-OH (DAMGO) is augmented in rats sustaining dopamine depletions. GABAergic projections from the nucleus accumbens to ventral pallidum and ventral tegmental area (VTA) are involved because stimulation of GABAB receptors in the VTA (by baclofen) or GABAA receptors in the ventral pallidum (by muscimol) inhibit the motor response induced by the microinjection of DAMGO into the nucleus accumbens. The present study was done to determine which of these projections is mediating the augmented DAMGO-induced motor activity that follows 6-hydroxydopamine lesions of the nucleus accumbens. The inhibition of DAMGO-induced activation by pallidal injections of muscimol was markedly attenuated in lesioned animals, whereas the inhibition by VTA injections with baclofen was greatly enhanced. A similar switch in emphasis from pallidal to mesencephalic efferents was not observed for dopamine-induced motor activity, because muscimol microinjections inhibited the response elicited by dopamine microinjection into the nucleus accumbens in all subjects. The stimulation of mu-opioid receptors in the ventral pallidum also elicits motor activation, and this is blocked by baclofen microinjection into the VTA. However, after dopamine depletion in the nucleus accumbens, baclofen in the VTA was ineffective in blocking the motor response by DAMGO in the ventral pallidum. These data reveal that dopamine depletion in the nucleus accumbens produces a lesion-induced plasticity that alters the effect of mu-opioid receptor stimulation on efferent projections from the nucleus accumbens and ventral pallidum.
In order to study central neuronal components involved in subcutaneous (s.c.) bee venom-induced persistent pain (a new tonic pain model), we use Fos immunostaining technique to study the spatial and temporal patterns of neuronal activity in the spinal cord of anesthetized rats. Following intraplantar bee venom injection, Fos-like immunoreactive (ir) neurons were only seen from L1 to S3 rostrocaudally with distinct distribution at L4-5 segments. At segments of L1-2 and S1-3, Fos-ir labelings were diffusely and symmetrically distributed on both sides of the gray matter; however, at L4-5 segments, Fos-ir neurons were densely localized in medial portion of laminae I-II, less densely in laminae V-VI and a few in laminae VII and X ipsilateral to the injection side. No Fos labeling was seen in ventral horn of the spinal cord at L4-5 segments. Fos protein began to express only within lamina I at 0.5 h, but increased over the whole dorsal horn at 1 h and reached peak labeling at 2 h after bee venom. Expression of c-Fos in laminae I-II decreased at 4 h, and completely disappeared at 24 h, however, labeling in laminae V-VI disappeared much slowly and existed even at 96 h after bee venom. Within laminae III-IV, Fos-ir neurons could not be seen at 0.5 h, but began to be seen at 1 h and appeared to exist even at 24 h after bee venom. Systemic morphine suppressed c-Fos expression dose-dependently in both superficial and deep layers of dorsal horn and the latter region was much more sensitive to morphine than the former one. The present results demonstrated that prolonged neuronal activities in superficial and deep layers of dorsal horn were essential to mediation of bee venom induced tonic pain and may have different roles in generation and/or modulation of spontaneous pain and hyperalgesia and allodynia.
In this study, mice received a single intracerebroventricular (i.c.v. ) injection of an antisense oligodeoxynucleotide (ODN) directed towards the mRNA of Gialpha2. Controls received a saline or a nonsense ODN injection. The subsequent effects on protein levels and mRNA of Gialpha2 were determined in mouse striatum, as well as, the effect on opioid ([d-Ala2, d-Leu5]-enkephalin; DADLE) inhibition of cyclic AMP (cAMP) formation in striatum and morphine analgesic potency. At 48 h after treatment, maximal inhibition (Emax) of cAMP formation was significantly reduced for the antisense group compared to controls. Antisense ODN treatment only changed the Emax and did not significantly alter the IC50s of the dose-effect curves for inhibition of cAMP formation. Antisense ODN, but not nonsense ODN, significantly reduced morphine's analgesic potency by >2-fold, 48 h following treatment. Using a quantitative immunoblotting procedure, antisense treatment was shown to decrease striatal Gialpha2 protein 48 h after antisense injection, while there were no changes in protein levels at 2, 12 and 24 h. In contrast, no changes in Gialpha2 mRNA in mouse striatum were noted at any time after antisense treatment. Taken together, these data suggest that Gialpha2 mediates opioid-induced analgesia and opioid inhibition of cAMP production in the mouse. These data also suggest that antisense reduces target protein by a mechanism independent of changes in mRNA abundance.