Systemic and microiontophoretic administration of morphine differentially effect ventral pallidum/substantia innominata neuronal activity

Abstract

In vivo electrophysiological recording techniques were employed to examine responses of ventral pallidum/substantia innominata (VP/SI) neurons to systemic and local administration of morphine. Using a cumulative dosing protocol, intravenous administration (0.1-30 mg/kg i.v.) produced a suppression of firing in 82% of neurons tested. The suppression was dose-related and blocked by the opioid antagonist, naloxone. In contrast, microiontophoretic applications of morphine resulted in current-related suppression (32% of neurons tested) or excitation (26%). Concurrent application of naloxone attenuated or blocked both effects of local morphine application. It was demonstrated that acute tolerance did not develop with repeated morphine exposures following either systemic or local administration. The present findings establish the sensitivity of VP/SI neurons to morphine and provide functional relevance at the level of a single neuron for opioid peptides and their receptors in this region. As reported for most other opioid-receptive brain areas, neuronal rate suppression was the predominate response observed, and it is proposed that excitations to iontophoresed morphine reflect a disinhibitory phenomenon. The differential morphine-induced rate changes, and number of responding neurons, observed with systemic vs. iontophoretic morphine administration suggest that extra-VP/SI regions that also are opioid sensitive can subsequently direct neuronal responsiveness to opioids within the VP/SI.

Lateral preoptic and ventral pallidal roles in locomotion and other movements

“…Despite resulting from bilateral VP bic infusions, pivoting in one direction or the other typically predominated, but it was almost always accompanied by fewer pivots in the opposite direction and, occasionally, an about even split between the two directions was observed. While we observed no frankly asymmetrical locomotor responses after unilateral VP bic infusions, others have reported wide turning after unilateral VP infusions of opioids (Hoffman et al, 1991; Napier, 1992; Napier et al, 1992) and musc (Kitamura et al, 2001). However, the latter, due to their reported large diameter (>30 cm) and relatively low frequency (about 4 turns/5 minutes max), may have been disrupted by or otherwise gone undetected in our square, 43 cm × 43 cm test space.…”

Opioid Modulation of Ventral Pallidal Inputs

“…3). 16‐18 The responses were blocked by naloxone (Fig. 3), verifying that opioid receptors were involved in both response types.…”

“…These results verify that an acute desensitization (i.e., tachyphylaxis) did not contribute to the pharmacological profile of the response obtained with rapidly repeated morphine injections. (Napier et al 18 With permission from John Wiley & Sons, Inc.)…”

Presynaptic Versus Postsynaptic Localization of μ and δ Opioid Receptors in Dorsal and Ventral Striatopallidal Pathways

“…Therefore, if postsynaptic receptors are mediating the observed stimulatory and /or inhibitory effects of locally administered morphine on enkephalin release in the pallidum (Olive and Maidment, 1996), it is necessary to invoke polysynaptic feedback mechanisms. In this regard, electrophysiological studies have reported both excitatory and inhibitory responses of V P neurons to microiontophoretic application of morphine (Napier et al, 1992;Chrobak and Napier, 1993;Mitrovic and Napier, 1995;Johnson and Napier, 1997) and primarily inhibitory responses of GP neurons (Huffman and Felpel, 1981;Stone, 1983;Napier et al, 1983Napier et al, , 1992.…”