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Alterations in brain opiate receptor mechanisms on proestrous afternoon
1Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville.
Abstract:
We have previously observed that gonadal steroid treatments, which stimulate a proestrous-like LH surge is ovariectomized rats, cause a marked reduction in the responsiveness to opiates of a variety of CNS processes. The present study was undertaken to determine if a similar decline in opiate responses is associated with the endogenous steroid-induced LH surge on the afternoon of proestrous. Rats were evaluated for thermic, nociceptive, behavioral and LH secretory responses to morphine sulfate on diestrous I afternoon (DiPM) and proestrous morning (ProAM), times at which LH secretion is low, as well as on proestrous afternoon (ProPM) during the preovulatory LH surge. While on DiPM and ProAM, morphine caused a 33-45% reduction in serum LH levels at doses as low as 5 mg/kg b.w., in ProPM rats doses as high as 10 mg/kg did not affect LH secretion. Similarly, ProAM rats showed a prompt and sustained analgesic response to morphine, but ProPM rats showed a delayed response of shorter duration. DiPM rats showed an acute response intermediate to that of ProAM and ProPM animals. While DiPM and proAM rats exhibited the expected hypothermic response to a high dose of morphine (15 mg/kg), ProPM rats showed no decline in core body temperature, but exhibited a delayed hyperthermic response to the opiate. DiPM and ProAM rats showed a dose-dependent decline in locomotor behavior in response to morphine. In contrast, ProPM rats, which exhibited a significantly elevated basal locomotor activity, failed to show a reduction in locomotion after morphine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
The natural luteinizing hormone (LH) surge in female rats significantly reduces their response to morphine, affecting pain, temperature, and behavior. This contrasts with responses during low LH periods, indicating hormonal influence on opiate sensitivity.
Area of Science:
- Neuroendocrinology
- Pharmacology
Background:
- Gonadal steroid treatments can reduce opiate responsiveness in rats.
- The endogenous luteinizing hormone (LH) surge during proestrus may also alter opiate sensitivity.
Purpose of the Study:
- To investigate if the endogenous LH surge affects opiate responses in rats.
- To compare opiate sensitivity during low LH periods versus the preovulatory LH surge.
Main Methods:
- Rats were tested for thermic, nociceptive, behavioral, and LH secretory responses to morphine sulfate.
- Responses were evaluated on diestrous I afternoon (DiPM), proestrous morning (ProAM), and proestrous afternoon (ProPM) during the LH surge.
Main Results:
- Morphine reduced LH levels during DiPM and ProAM but not during the ProPM LH surge.
- Analgesic and thermic responses to morphine were diminished and delayed during the ProPM LH surge.
- Locomotor activity was not reduced by morphine in ProPM rats, unlike in DiPM and ProAM rats.
Conclusions:
- The preovulatory LH surge significantly attenuates central nervous system (CNS) responses to morphine in rats.
- Hormonal fluctuations, specifically the LH surge, play a critical role in modulating opiate effects.