Lack of involvement of delta-opioid receptor in mediating physical dependence at the hypothalamus-pituitary-adrenocortical (HPA) axis in the rat.
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.
Gonzalvez
M L
ML
Department of Physiology and Pharmacology, University School of Medicine, Murcia, Spain.
Vargas
M L
ML
Milanés
M V
MV
D000818:Animals; D003345:Corticosterone / Q000097:blood; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009293:Opioid-Related Disorders / Q000209:etiology*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000502:physiology*
D004745:Enkephalins; D017465:Receptors, Opioid, delta; D004743:Enkephalin, Leucine; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D003345:Corticosterone