Enduring effects of morphine pellets revealed by conditioned taste aversion

Abstract

Morphine pellets (75 mg) were implanted subcutaneously in albino rats. Three days later, following 24 h without water, these rats (Group MSN) were given access to a saccharin solution for 30 min, then injected with naloxone hydrochloride. The classical abstinence signs, including "wet dog shakes"and weight loss, were noted in these subjects, but not in controls given placebo pellets and /or saline injections. In addition, when given an opportunity to drink either saccharine solution or water 24 h later, Group MSN rats drank significantly less saccharin than any of the control groups. Similar drinking patterns were found even when naloxone injection was delayed as long as 3 weeks after pellet implantation, when none of the classical abstinence signs were seen and serum levels of morphine and its metabolites were 100 times lower according to radioimmunoassay. This simple and objective technique is thus more sensitive as a measure of prior morphine exposure than any of the commonly used indices. The continued utility of a dependent-nondependent dichotomy is also examined in light of these and other findings.

Chronic morphine treatment exaggerates the suppressive effects of sucrose and cocaine, but not lithium chloride, on saccharin intake in Sprague-Dawley rats.

“…Indeed, although we were not able to evaluate the brains of the rats in the present experiments, we have verified that this morphine-treatment regimen does in fact lead to a reduction in neurofilament protein and to an increase in glial fibrillary acidic protein in the VTA (Wheeler, Levison, & Grigson, 2000). Interestingly, both a history of chronic morphine treatment and the ensuing neurochemical characteristics have been associated with withdrawal (Guitart et al, 1993; Manning & Jackson, 1977) and with the increase in responsiveness to the rewarding properties of drugs of abuse (Horger et al, 1990; Kosten et al, 1997; Lett, 1989). Thus, the data suggest that chronic morphine treatment may modify cells in the VTA–NAc pathway and, in so doing, sensitize the rat to the rewarding properties of the US.…”

Chronic morphine reduces pain-related disability in a rodent model of chronic, inflammatory pain.

“…Unfortunately, tolerance seems to develop more quickly to the beneficial analgesic effects of morphine than to the adverse effects of morphine (Solomon, Wasserman, & Gebhart, 1987). Subcutaneous morphine pellets were originally developed to study tolerance, dependence and withdrawal, and addiction, and numerous researchers have reported that continuous morphine from subcutaneous pellets rapidly produced tolerance and dependence (Bhargava & Villar, 1991; Gellert & Sparber, 1977; Manning & Jackson, 1977; Meyer & Sparber, 1976; Riffee et al, 1980; Young & Thompson, 1979). Morphine was shown to reduce the rate of bar pressing in normal rats (Hill, Pescor, Belleville, & Wikler, 1957), and previous work in our own lab demonstrated that acute morphine injections impaired performance of normal rats in the delayed matching-to-position task (Lindner et al, 1997).…”

Extinction of conditioned opiate withdrawal in rats in a two-chambered place conditioning apparatus

“…These include modulation of operant responding for food, morphine, heroin, or brain stimulation reward 7-9 and avoidance of the withdrawal-paired cue or context 10-13 . Avoidance of the withdrawal-paired cue is often demonstrated using opiate withdrawal-induced conditioned place aversion (OWCPA), which is a popular measure because of its simplicity.…”