Electrophysiological studies on the postnatal development of the spinal antinociceptive effects of the delta opioid receptor agonist DPDPE in the rat

Abstract

1 The antinociceptive e ects of the delta opioid receptor selective agonist, DPDPE [(D-Pen 2 ,DPen 5 )-enkephalin] was studied in rats aged postnatal day (P) 14, P21, P28 and P56.2 Antinociceptive e ects of DPDPE were measured as percentage inhibition of the C-®bre evoked response and post-discharge of dorsal horn neurones evoked by peripheral electrical stimulation. DPDPE was administered by topical application, akin to intrathecal injection. 3 DPDPE (0.1 ± 100 mg) produced dose-related inhibitions at all ages; these inhibitions were reversed by 5 mg of the opioid antagonist naloxone. 4 The dose-response curves for C-®bre evoked response and post-discharge of the neurones were not di erent in rats aged P14 and P21. DPDPE was signi®cantly more potent at P14 and P21 compared with its inhibitory e ects on these responses at P28 and P56. 5 DPDPE produced minor inhibitions of the A-®bre evoked response of the neurones at P14, P21, P28 and P56, suggesting that the inhibitory e ects of DPDPE are mediated via presynaptic receptors on the terminals of C-®bre a erents. 6 Since spinal delta opioid receptor density changes little over this period, the increased antinociceptive potency of DPDPE in the rat pups compared with the adult is likely to be due to post-receptor events, or in developmental changes in the actions of other transmitter/receptor systems within the spinal cord.

Respiratory function in adult mice lacking the µ‐opioid receptor: role of δ‐receptors

“…In MOR –/– mice, an alternative explanation for the mismatch between the ineffectiveness of δ‐receptor agonists on respiration in vivo (Matthes et al ., 1998) and their effectiveness in vitro , is that this difference might arise from developmental receptor changes between juvenile (15–30‐day‐old) slices and fully mature adults in vivo , rather from different target structures. Although there are well documented increases in the density of opioid receptors in the whole rodent brain during this time frame (Kitchen et al ., 1995; Negri et al ., 1997), such an increase is not homogenous in all brain structures (Rahman & Dickenson, 1999) and notably in brainstem respiratory areas where the density of δ‐binding sites reaches maximal levels at postnatal day 21 (Xia & Haddad, 1991). Furthermore, the density of δ‐binding sites is not always correlated with the physiological potency of δ‐receptor agonists in the same structures (Rahman & Dickenson, 1999).…”

“…Although there are well documented increases in the density of opioid receptors in the whole rodent brain during this time frame (Kitchen et al ., 1995; Negri et al ., 1997), such an increase is not homogenous in all brain structures (Rahman & Dickenson, 1999) and notably in brainstem respiratory areas where the density of δ‐binding sites reaches maximal levels at postnatal day 21 (Xia & Haddad, 1991). Furthermore, the density of δ‐binding sites is not always correlated with the physiological potency of δ‐receptor agonists in the same structures (Rahman & Dickenson, 1999). It is also unlikely that δ‐receptors lose their efficacy in brainstem respiratory structures with age, which supports the hypothesis that respiratory‐depressing target areas are located outside these structures.…”

δ-Opioid Receptor Function in the Dorsal Striatum Plays a Role in High Levels of Ethanol Consumption in Rats

“…The developmental decrease in TAN67-mediated analgesia is comparable to age-related reductions in spinally administered DPDPE-mediated analgesia (Crisp et al, 1994a,b;Rahman and Dickenson, 1999). Although binding studies revealed no age-related changes in receptor density or affinity in the spinal cord (Hoskins et al, 1998;Rahman et al, 1998), our studies show a developmental decrease in DOP-R activity in the dorsal striatum using the [ (Cichewicz et al, 2004;Narita et al, 2007), caudate nucleus, and nucleus accumbens (Saland et al, 2004), consistent with our findings of low DOP-R coupling in the dorsal striatum of aged rats.…”

Endogenous Opioids and Their Role in Stem Cell Biology and Tissue Rescue

“…Since these small peptides have a short half-life both in vivo and in vitro, researchers also use synthetic forms of enkephalins, which are much more stable. Among them, the most common are DAMGO ([D-Ala 2 , N-MePhe 4 , Gly-ol]-enkephalin) [ 17 , 18 ], DPDPE ([D-Pen 2 , D-Pen 5 ]-enkephalin) [ 19 , 20 ], and DADLE ([D-Ala 2 , D-Leu 5 ]-enkephalin) [ 21 , 22 ].…”