Endogenous opioids and their role in odor preference acquisition and consolidation following odor–shock conditioning in infant rats

Abstract

We assessed the neurochemical basis of olfactory learning induced by presentations of odor and moderate shock in infant rats. Paradoxically, shock conditioning produces an odor preference in 8-day-olds, but an odor aversion in 12-day-olds. Studies have demonstrated the importance of opioids in early olfactory learning; their specific role remains undefined. In this study, postnatal Days 8 and 12 pups were systemically injected with naltrexone, a nonspecific opioid antagonist, or saline and received either paired or backward presentations of odor-moderate shock or odor-only presentations. Blocking the opioid system during conditioning disrupted acquisition of the Day 8 odor preference, but not the Day 12 odor aversion. Additional Day 8 pups were given naltrexone posttraining. Naltrexone not only blocked consolidation of an odor preference but also yielded an odor aversion. These results suggest that the opioid system has a critical role in both olfactory learning and consolidation of odor preferences during the sensitive period.

Acquisition and expression of a socially mediated separation response

“…Naltrexone administration blocks the formation and consolidation of odor learning in 12 day-old rats, but not its expression [88,89]. Such a role is also suggested by the report that μ-receptor knockout mice do not potentiate USV to their dams [69].…”

“…Orpm−/− mouse pups emit fewer vocalizations during an initial isolation; do not show a preference for maternal cues; and do not show USV potentiation following brief reunions. As μ-opioid activity does not regulate USV potentiation in rats [91] nor expression of odor learning at PND12 [88,89], we hypothesize that the knockout mice have a deficit in the acquisition of a strong social bond, rather than with the expression.…”

Examining the role of endogenous opioids in learned odor–stroke associations in infant rats

“…Thus, neonates display unique learning characteristics about pain. Using this paradigm, we have shown that opioid receptor antagonism during neonatal odor-shock conditioning prevents acquisition of a conditioned odor preference (Roth & Sullivan, 2001). In sharp contrast, opioid receptor antagonism immediately following the odor-shock conditioning produces an odor aversion instead of the typical odor preference (Roth & Sullivan, 2001.…”

“…Endogenous opioids have been shown to play a prominent role in the postnatal attachment process. Specifically in the rat neonate, opioids facilitate odor preference learning (Barr & Rossi, 1992;Kehoe & Blass, 1986a;Panksepp, Nelson, & Siviy, 1994;Randall, Kraemer, Dose, Carbary, & Bardo, 1992;Roth & Sullivan, 2001Shide & Blass, 1991), and nipple-milk conditioning (Petrov, Varlinskaya, Becker, & Smotherman, 1998, Petrov, Varlinskaya, & Smotherman, 2000Robinson, Arnold, Spear, & Smotherman, 1993;Robinson & Smotherman, 1997). Suggestive of their rewarding value in neonates, opioids are sufficient to alleviate separation distress (Carden, Barr, & Hofer, 1991;Goodwin, Molina, & Spear, 1994;Kehoe & Blass, 1986b;Panksepp, Herman, Conner, Bishop, & Scott, 1978).…”

“…Pups received 0.5 mg/kg of NTX (Kehoe & Blass, 1986a;Roth & Sullivan, 2001 and were given 15 min to recover undisturbed in a 30 C incubator before beginning odor-stroke conditioning. For Experiment 2, pups received 0.5 mg/kg of NTX or equal volume saline (SAL; subcutaneous at the nape of the neck) immediately following the end of odor-stroke conditioning.…”