Increased opioid receptor binding and G protein coupling in the accumbens and ventral tegmental area of postnatal day 2 rats

Abstract

In some regions of the developing rat brain such as the nucleus accumbens (Acb), mu opioid (MOP) receptor specific binding in the perinatal period exceeds that in the adult. To investigate the significance of these developmental changes, MOP and nociceptin/orphanin FQ (NOP) receptor binding and G protein coupling as determined by GTPγS binding experiments were examined in mesolimbic regions of postnatal day 2 (P2) pups and compared to those of their dams. Acb of the P2 pup exhibited 2-fold greater MOP receptor specific binding than that of the dam. In the ventral tegmental area (VTA), NOP specific binding was about 2-fold higher in the P2 pup. A correlation was found between MOP and NOP binding and their coupling to G protein on dam and P2 pup brain sections. However, the magnitude of increases in MOP and NOP receptor G protein coupling to G protein in P2 pups exceeded the 2-fold differences in binding between pups and dams. Furthermore, the amplitude of the MOP receptor G protein coupling in female P2 Acb was greater than increases in male P2 pup Acb. Differences in MOP and NOP binding and G protein coupling in other mesolimbic regions between P2 pups and dams were rarely observed. The data indicate that greater binding and G protein coupling of MOP and NOP receptors occur in discrete, mesolimbic regions of P2 pups when compared to their dams. It may be of significance that these brain regions, Acb and VTA, are undergoing maturation on P2. KeywordsDevelopment; Nociceptin; Mu opioid receptor; Mesolimbic region; Cortex; Nociceptin receptor Opioid receptors and their endogenous ligands have been detected in rodent brain beginning as early as the second week of gestation [4,5,10,15,21,22,25,26]. In experiments where forebrain opioid receptor binding densities were measured by in vitro binding assays, it was determined that the number of opioid receptor binding sites increases with age. When selective ligands were used in such studies, a differential ontogeny for μ (MOP), δ (DOP) and κ (KOP) receptors was discovered. Forebrain MOP and KOP binding was detectable in the prenatal period, whereas DOP binding was detectable only in the second postnatal week [10,15,22,25,26,28]. Interestingly, when MOP binding density in rodent forebrain was measured with respect to protein instead of wet tissue weight, its binding density was higher in the prenatal interval [15,22], but declined in the postnatal period [25,26] [11,29]. In support of this possibility, DAMGO stimulation of GTPγS binding has been detected in mouse brain as early as embryonic day 12.5, a time at which MOP receptor is also detected [19,22].The newest member of the opioid receptor family is the NOP receptor. NOP receptor binding and G protein coupling are abundant in the cerebral cortex and some limbic regions of the adult rodent and primate brain as shown by autoradiographic methods [3,6,9,13,23,24]. Although the ontogeny of NOP receptor mRNA expression has been studied [9,17], its binding and G protein coupling capacity in brain during development ha...

Endogenous opiates and behavior: 2009

“…Pairing Dyn and suckling on a nipple increased responsiveness 1 day later, indicating conditioning (905). MOR and ORL-1 receptor binding are significantly and respectively increased in the NAC and VTA of two-day old rat pups relative to their dams, effects attributable to increased G-protein coupling which in turn showed greater effects in female relative to male pups in the NAC (483). Neonatally-handled male mice display greater body weights, increased plasma ACTH and corticosterone and decreased hypothalamic ACTH and CRF as adults, effects blocked by neonatal administration of AS directed against POMC (379).…”