Medial forebrain stimulation enhances intracranial nociception and attenuates morphine analgesia suggesting the existence of an endogenous opioid antagonist

Abstract

The purpose of this experiment was to test in the rat the hypotheses that activation of the brain reward system would attenuate the effects of intracranial nociceptive stimulation and would potentiate the antinociceptive effects of morphine. In this experiment pain (nociception) was generated by electrical stimulation of a brain pain pathway, the mesencephalic reticular formation (MRF) of the rat. Reward pathway stimulation was to the medial forebrain bundle at the level of the lateral hypothalamus (MFB-LH). Current thresholds for escape from MRF stimulation were determined using a modification of the psychophysical methods of limits. MRF stimulation was delivered concurrently with different intensities of non-contingent MFB-LH stimulation. The effects of morphine and saline were determined under all stimulation conditions. Contrary to expectation MFB-LH stimulation significantly lowered MRF stimulation escape thresholds. Morphine administration elevated MRF thresholds in the absence of MFB-LH stimulation. However, this effect was blocked by concurrent MFB-LH stimulation. These findings, which mimic the effects of the opiate antagonist naloxone, i.e., potentiating of pain and antagonism of morphine’s analgesic effects, suggest the presence of an endogenous opiate receptor antagonist.

Bilateral responses of rat ventral striatum tonically active neurons to unilateral medial forebrain bundle stimulation

“…Unilateral stimulation of the MFB effectively promotes reinforcement learning (Corbett & Wise, 1980; Hermer‐Vazquez et al., 2005; Hodos & Valenstein, 1962; Kornetsky, Knapp, Tozier, & Pak, 2010; Lee et al., 2010; Mueller, Huston, & Pritzel, 1981; Olds & Milner, 1954; Reynolds, 1958; Schaefer, West, & Michael, 1987; Talwar, Xu, Hawley, Weiss, et al, 2002; Xu, Talwar, Hawley, Li, & Chapin, 2004). The drive to obtain this artificial reinforcer can cause animals to press a lever inducing MFB stimulation (also referred to as intracranial self‐stimulation) to the extent of disregarding primal physiological needs of natural reinforcers such as food or water (Olds & Milner, 1954).…”