UBC Theses and Dissertations
The role of opioid receptors in lordosis behaviour Pfaus, James George
Opioid agonists such as heroin, morphine, methadone, Met⁵-enkephalinamide, and β-endorphin have been shown to inhibit sexual behaviour in a variety of mammalian species. Although an extensive literature exists on the neuroendocrinology of opioid administration, little is known about the role of individual opioid receptors in the inhibition of sexual behaviour. This lack of information is due, in large part, to the lack of opioid receptor selectivity of the drugs used to study sexual behaviour. Accordingly, the present experiments assessed the dose-response and time-course effects of several selective opioid peptides, administered intracerebroventricularly (icv), on the lordosis behaviour of ovariectomized rats rendered sexually receptive by estrogen and progesterone. In Experiments 1 through 4, lordosis behaviour was assessed in each female rat 15, 30, 60, 90, and 120 min after the infusion of different doses of a selective peptide. In Experiment 5, lordosis behaviour was measured 60 min after the infusion of effective doses of each of the peptides studied in the preceding experiments. In Experiment 1, the effect of μ/δ receptor activation was assessed using β-endorphin. β-endorphin produced a dose-dependent dual effect on lordosis behaviour; a low dose (200 ng) significantly inhibited lordosis, whereas a higher dose (2000 ng) produced a significant facilitation. Experiment 2 examined the effect of the selective u receptor agonist, mbrphiceptin, on lordosis behaviour. Morphiceptin also produced a dose-dependent dual effect in which the lowest dose (20 ng) significantly inhibited, whereas the two higher doses (200, 2000 ng) significantly facilitated lordosis. In Experiment 3, the selective δ receptor agonist, δ-receptor peptide, significantly facilitated lordosis behaviour at all doses. In contrast, in Experiment 4 the selective K receptor agonist, dynorphin 1-9, had no significant effect on lordosis behaviour. Finally, in Experiment 5, the ability of the opioid receptor antagonist naloxone to reverse the effects of β -endorphin, morphiceptin, and δ -receptor peptide observed in the first four experiments was determined. The effects of each peptide were replicated and were reversed by naloxone, indicating that the effects observed in the first four experiments were reliable and that they were produced by the activation of opioid receptors. Naloxone alone, however, had no effect on lordosis behaviour. These results indicate that the selective activation of opioid receptors differentially affects lordosis behaviour in female rats. It appears that binding to high-affinity μ₁receptors exerts an inhibitory influence on lordosis, whereas binding to low-affinity μ₂ receptors or δ receptors exerts a facilitatory influence. Binding to K receptors does not appear to affect lordosis behaviour. The failure of naloxone alone to affect lordosis behaviour suggests that endogenous opioid systems do not exert a tonic inhibitory or facilitatory influence in ovariectomized rats primed with estrogen and progesterone. The present experiments demonstrate the importance of using highly selective opioid receptor ligands in the study of the behavioural effects of opioid drugs.