Brain research
-
Chronic opiate exposure leads to maladaptive changes in brain function. In view of the localization of opiate receptors in mammalian visual system, chronic opiate exposure is likely to affect the visual responses properties of V1 neurons. ⋯ However, re-exposure with morphine could significantly improve the function of V1 neurons in morphine-treated cats. These findings demonstrated that chronic morphine treatment could significantly degrade the response properties of V1 neurons and may lead to a function dependence on morphine in visual cortical cells.
-
Comparative Study
Intermittent dosing prolongs tolerance to the antinociceptive effect of morphine microinjection into the periaqueductal gray.
Tolerance to the antinociceptive effect of microinjecting morphine into the ventrolateral periaqueductal gray (vPAG) develops with repeated administration. The objective of the present experiment was to determine whether the magnitude and duration of tolerance differ depending on the interval between injections. Rats were injected with morphine or saline into the vPAG either once daily for 4 days or twice daily for 2 days. ⋯ That is, tolerance was evident 2 weeks following the induction of tolerance produced by daily, but not twice daily injections of morphine. Although a long inter-dose interval has been shown to prolong the duration of tolerance after systemic morphine administration, this is the first report showing a similar effect with direct administration of morphine into the brain. Given that associative learning underlies prolonged tolerance with systemic morphine administration, the present data suggest that associative mechanisms of tolerance are also engaged when morphine administration is restricted to the PAG.
-
Comparative Study
Reduced suppression of CO2-induced ventilatory stimulation by endomorphins relative to morphine.
Opioids are among the most effective analgesics, but a major limitation for their therapeutic usefulness is their induction of respiratory depression. Endomorphin-1 (EM1), in contrast to several other mu opioids, exhibits a threshold for respiratory depression that is well above its threshold for analgesia. Its effect on sensitivity to CO(2), however, remains unknown. ⋯ EM1 and EM2 attenuated the hypercapnic ventilatory response (HCVR) only in high doses, while DAMGO and morphine diminished the HCVR in much lower doses. The ventilatory effects of high doses of all 4 agonists were blocked by the mu-opioid antagonist naloxone (0.4 mg/kg i.v.), but not by the peripherally restricted mu-opioid antagonist, methyl-naloxone (0.4 mg/kg i.v.). It was concluded that the endomorphins attenuated the HCVR only in large doses, well beyond the analgesic threshold, and did so through a centrally mediated mu-opioid mechanism.
-
A retrograde tracer, WGA-apo-HRP-gold (WG), was injected into each subdivision of the dorsal raphe (DR) nucleus, and subsequent orexin-A immunostaining was performed for the tuberal region of the hypothalamus in order to investigate orexin projections to the DR. Similar to previous studies, the majority of orexin-single-labeled neurons were observed at the dorsal half of the lateral hypothalamus (LH), the circle around the fornix, i.e., perifornical nucleus (PeF), and the area dorsal to the fornix. The present study reports that hypothalamic neurons exhibited differential projections to each subdivision of the DR. ⋯ Only a few double-labeled cells were observed in dorsomedial and posterior hypothalamic nuclei. Our observations suggest that various hypothalamic neurons differentially project to each subdivision of the DR, a portion of which is orexin-immunoreactive. These orexin-immunoreactive DR-projecting hypothalamic neurons might have wake-related influences over a variety of brain functions subject to DR efferent regulation, including affective behavior, autonomic control, nociception, cognition, and sensorimotor integration.
-
Behavior studies have demonstrated that local application of morphine in peripheral tissues resulted in a significant antinociceptive effect, but there has been no electrophysiological evidence to support the peripheral mechanism of opioid antinociception. The purpose of the present study was to investigate whether local application of morphine suppressed the glutamate-evoked activities of C and Adelta primary afferent fibers in dorsal hairy skin of rat in vivo. The single unit activities of the C and Adelta afferent fibers were recorded by means of isolation of the fiber filaments from the dorsal cutaneous nerve branches, and the effects of glutamate and glutamate plus morphine injected into the receptive field on these activities were determined. ⋯ The mean discharge rates of C fibers and Adelta fibers decreased from 28.96 +/- 6.85, 28.99 +/- 3.79 impulses/min to 4.40 +/- 1.76, 2.72 +/- 0.71 impulses/min, respectively. The suppressing effect of morphine was reversed by pretreatment with opioid receptor antagonist naloxone (1.0 mM). These findings suggest that local application of morphine can suppress the glutamate-evoked activities of the fine fibers in rat hairy skin and thus provide an electrophysiological evidence for peripheral antinociception of opioids.