PubMed · 8983898
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C Mignat. 1996-11-22. [Morphine].. https://doi.org/10.1055/s-0029-1234191
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The effect of chronic nicotine administration on (1) antinociception; (2) opioid receptor binding; and (3) met-enkelphalin levels in discrete brain regions in rats was investigated. Male and female Sprague-Dawley rats were treated with nicotine 0.3 mg/kg, 0.1 mg/kg, or saline three times a day subcutaneously during a 14-day protocol. Antinociception was measured by hotplate (HP) test on days 1, 2, 7, 10 and 14. After completion of the protocol, mu-opioid receptors were analyzed by [3H]-DAMGO binding studies and met-enkelphalin levels were determined by radioimmunoassay. Results indicated that hot-plate latency increased during the first 2 days of nicotine administration for male and female rats who were treated with 0.3 mg/kg nicotine. There was an up-regulation of mu-receptors (increased Bmax) in the striatum of rats treated with 0.3 mg/kg nicotine, compared to 0. 1 mg/kg nicotine and saline groups. An interaction effect of group by gender was noted. After 14 days of chronic nicotine administration, met-enkelphalin levels were significantly lower in striatum and midbrain of animals treated with 0.3 mg/kg nicotine, as compared to controls. These results suggest that chronic nicotine administration, in doses representative of human smoking, produces antinociception initially, and is accompanied by an upregulation of micro-opioid receptors in the striatum of rats. In addition, nicotine-induced tolerance to antinociception may be associated with a decrease in met-enkelphalin level over a period of time.
The cellular mechanisms underlying mu opioid facilitation of mossy fiber (MF) long-term potentiation (LTP) and synaptic transmission were investigated in the rat hippocampal slice. Naloxone (10 microM) significantly inhibited the induction of mossy fiber LTP, an effect attributed by Derrick and Martinez [B.E. Derrick, J.L.J. Martinez, Opioid receptor activation is one factor underlying the frequency dependence of mossy fiber LTP induction, J. Neurosci. 14 (1994) 4359-4367] to antagonism of endogenous opioid peptide action. We found that the inhibitory effects of naloxone were not blocked by bicuculline, suggesting that endogenous opioids did not enhance mossy fiber LTP by depressing GABAA inhibition. [d-Ala2, NMePhe4, Glyol5] enkephalin, DAMGO (300 nM), a mu opioid agonist, mimicked the action of endogenous opioids, enhancing both mossy fiber LTP induction and paired-pulse facilitation. DAMGO potentiation of the paired-pulse facilitation of mossy fiber response was also insensitive to bicuculline but was blocked by the mu selective antagonist CTOP. Further analysis of the cellular mechanism showed that the depletion of internal Ca2+ stores by thapsigargin (1 microM), or inhibition of protein kinases by application of staurosporine (1 microM) did not block the DAMGO facilitation of mossy fiber-CA3 synaptic transmission. However, application of phaclofen (100 microM GABAB receptor antagonist or SCH 50911, a more potent GABAB antagonist significantly inhibited the DAMGO effect (49+/-15%; 51+/-19% inhibition, P<0.05). The data indicate that the DAMGO effect on the mossy fiber pathway is partially mediated by a reduction in GABA activation of GABAB receptors. These findings further suggest that endogenous opioid peptides activate mu opioid receptors to facilitate mossy fiber LTP and synaptic transmission in rat hippocampus partially by GABAB receptor-mediated disinhibitory mechanism.
Sex differences have been observed in antinociception following central administration of morphine into either the lateral ventricles or rostral ventromedial medulla (RVM) such that male rats exhibit significantly greater antinociception than female rats. The present study examined whether sex and adult gonadectomy differences were observed in morphine-induced (1-10 micrograms) antinociception elicited from the ventrolateral periaqueductal gray (vlPAG) on two nociceptive measures. Both sham-operated (ED50=1.20-1.60 microgram) and castrated (ED50=1.08-1.09 micrograms) male rats displayed significantly greater magnitudes and potencies of morphine-induced antinociception on both tests than female rats. Sham-operated female rats tested during the estrous phase (ED50=>50 micrograms) were significantly less sensitive to morphine than ovariectomized female rats (ED50=1.98-2. 51 micrograms). Thus, the vlPAG, a site sensitive to interactions between estradiol-containing hypothalamic loci and opioid peptides, elicits morphine-induced antinociception which is sensitive to sex differences and adult gonadectomy.