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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Comparison of the effects of morphine on hypothalamic and medial frontal cortex self-stimulation in the rat
Abstract:
The effect of morphine (3.75, 7.5, and 15.0 mg/kg, s.c.) on medial frontal cortex (MF) and hypothalamic self-stimllation (SS) was determined 1, 3, 5, and 7 h after injection for 5 consecutive days. Morphine suppressed or enhanced SS responding as a function of dose, time after injection, and the site stimulated. The MF SS groups were less sensitive to the toxic effects of morphine, and evidenced elevated rates of responding earlier after injection than the hypothalimic animals. The dose-response relationship of the MF rats, thus, clearly differed from that of the hypothalamic rats. With repeated administration, tolerance was rapidly (3-4 days) developed to the suppressive effect while the excitatory effect appeared earlier and tended to be enhanced, peaking 1 and 3 h after injection in the MF and hypothalamic groups, respectively. These data provide additional evidence against the hypothesis that the effect of morphine on SS behavior is non-specific. If it were, the time course and degree of effects should be similar, regardless of the electrode site tested. Furthermore, an inhibitory effect was not observed in the groups receiving 3.75 mg/kg although both showed a significant increase in responding 1 and/or 3 h after injection. This observation indicates that the excitatory effect is not dependent on the depressant effect and, therefore, probably is not a rebound phenomenon. It also suggests that the toxic effects of morphine can either mask or delay the appearance of its facilitatory action on SS responding.
Insights
Morphine
Area of Science:
- Neuroscience
- Pharmacology
Background:
- The effects of morphine on brain stimulation reward are complex and depend on various factors.
- Previous research has not fully elucidated the specific mechanisms underlying morphine's influence on self-stimulation (SS) behavior at different brain sites.
Purpose of the Study:
- To investigate the dose- and time-dependent effects of morphine on medial frontal cortex (MF) and hypothalamic self-stimulation (SS) in rats.
- To examine the development of tolerance to morphine's effects with repeated administration.
- To differentiate between direct facilitatory and rebound inhibitory effects of morphine on SS.
Main Methods:
- Rats were trained to perform self-stimulation (SS) in either the medial frontal cortex (MF) or hypothalamus.
- Morphine was administered subcutaneously at doses of 3.75, 7.5, and 15.0 mg/kg for 5 consecutive days.
- SS responding was recorded 1, 3, 5, and 7 hours after each injection.
Main Results:
- Morphine produced dose- and time-dependent suppression or enhancement of SS responding, varying by brain site.
- Medial frontal cortex (MF) groups showed less sensitivity to toxic effects and earlier elevated responding compared to hypothalamic groups.
- Tolerance to morphine's suppressive effects developed rapidly (3-4 days), while excitatory effects emerged earlier and were enhanced.
Conclusions:
- Morphine's effects on SS behavior are site-specific, providing evidence against a non-specific action.
- The excitatory effect of morphine on SS is independent of its depressant effect, suggesting a direct facilitatory mechanism.
- Toxic effects of morphine can mask or delay its facilitatory actions on SS responding.
