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1. In previous studies, we have demonstrated that delta-opioid receptors are involved both in the acute control of hypothalamus-pituitary-adrenocortical (HPA) axis activity and in the development of neuroendocrine opioid tolerance. In the present work we studied whether central delta-opioid receptors play a role in the development of neuroendocrine physical dependence to opioids in the rat. 2. Intracerebroventricular (i.c.v.) administration of the delta-selective agonist DPDPE ([D-Pen2,D-Pen2]enkephalin) produced stimulation of HPA activity, as shown by an increase in corticosterone release. This effect was antagonized by i.c.v. co-administration of ICI 174,864, a selective delta-receptor antagonist, which provide direct evidence that the activation of the HPA axis produced by DPDPE is mediated by central delta-opioid receptor. 3. Chronic pretreatment with i.c.v. DPDPE resulted in tolerance to its neuroendocrine effect. Intracerebroventricular injection of ICI 174,864 to DPDPE-tolerant rats produced neither alteration in corticosterone release nor behaviour signs of dependence. 4. It was concluded that delta-opioid receptors do not play a role in the development of opioid neuroendocrine physical dependence at the HPA axis.

1. Modifications by stress of the effects of morphine on pituitary-adrenocortical activity were examined in the guinea-pig at different lengths of time. 2. An increase in plasma cortisol but not in beta-endorphin levels was obtained in guinea-pigs stressed for 60 min. 3. Morphine (50 mg kg i.p.) enhanced beta-endorphin and cortisol levels 5 min after injection and decreased beta-endorphin concentration 30 and 90 min after its administration. 4. In stressed guinea-pigs plasma beta-endorphin levels were reduced 5 min after morphine injection. 5. These results indicate that stress can alter the effects of morphine on pituitary-adrenal activity in the guinea-pig and that the type of modification may be dependent on the time of the sampling.

1. i.c.v. morphine administration (50 micrograms/10 microliters) to sham-lesioned guinea-pigs produces a decrease of body temperature 90 min after injections. 2. This effect was blocked in animals that received i.c.v. 6-OHDA injections 20 days before. 3. On the other hand, morphine injection to sham-lesioned guinea-pigs resulted 30 and 90 min later in suppressed plasma B-END and cortisol concentration. 4. This suppressive effect was increased 20 days after 6-OHDA injections. 5. These results indicate that in the guinea-pig the effects of morphine on both body temperature and plasma levels of B-END and cortisol are altered by hypothalamic DA lesions, and suggest that hypothalamic DA neurons would be one of the sites participating in morphine-induced delayed decreased in plasma B-END and cortisol.

1. Changes in plasma levels of B-END and cortisol were investigated in guinea-pigs receiving either stressful stimuli for various lengths of time or i.p. injections of morphine or saline. 2. A decrease in B-END levels occurred when animals were stressed, whereas cortisol was not affected. 3. Morphine (50 mg/kg i.p.) enhanced B-END and cortisol levels 5 min after injection, whereas a decrease in B-END was seen at 30 min. 4. Saline (i.p.) produced a decrease of B-END levels 30 min after injection and an increase in cortisol 5 and 10 min after injection. These findings suggest that in the guinea-pig the response of pituitary-adrenal axis to stress or morphine could change depending upon the time of sampling.

Morphine (30 mg/kg i.p.) produced a hypothermic effect in restrained rats which was antagonized by naloxone pretreatment (10 mg/kg s.c.). This hypothermia was inhibited by deprenyl pretreatment (5 mg/kg i.p.) and by beta-phenylethylamine treatment (25 mg/kg i.p.). However, the effect of morphine was partially potentiated when a higher dose of deprenyl (10 mg/kg i.p.) was administered. Pretreatment with clorgyline (1 mg/kg i.p.) potentiated the morphine-induced hypothermia. In contrast, the effect of morphine was antagonized when a higher dose of clorgyline was used (5 mg/kg i.p.). Based on these results, a possible role of brain serotonin and dopamine in the thermoregulatory effects of morphine is proposed in this paper.

Morphine 50 mg/kg i.p. produced a hypothermic effect in unrestrained guinea-pigs and this effect was potentiated when animals were restrained. The morphine-induced hypothermia was antagonized by dexamethasone treatment (1 mg/kg 24 hr and 0.5 mg/kg i.p. 2 hr before morphine). Treatment with the inhibitor of peptide biosynthesis cycloheximide (10 mg/kg i.p. 24 and 2 hr before morphine) also inhibited the hypothermic effect of morphine. ACTH injected intracerebroventricular produced no changes in body temperature. These results are consistent with the hypothesis that anterior pituitary peptide beta-endorphin may play a role in the hypothermic effect produced by morphine in the guinea-pig.