Associative factors in the effects of morphine on self-stimulation

Abstract

These experiments tested the hypothesis that the suppressing and facilitating effects of morphine on intracranial self-stimulation (ICS) (measured 1 h and 3 h post-injection, respectively) are influenced by associative, non-pharmacological factors. Experiment 1 confirmed previous demonstrations that the facilitation of ICS by morphine (10 mg/kg) develops with repeated drug exposures. Once ICS facilitation had developed, the effect was mimicked by saline injection in most subjects. In a separate group of animals, previous exposure to morphine in the home cage prevented drug-induced facilitation of ICS. Tolerance to ICS suppression developed after repeated pairings of the drug and the ICS chambers, but not when the drug had previously been received in the home cage. Experiment 2 examined the effect of low (0.3, 1, 3 mg/kg) doses of chronic morphine on ICS. Facilitation was observed with 1 and 3 mg/kg, but only after repeated testing. Naloxone (0.1 and 1 mg/kg) failed to reverse facilitation in a number of these subjects. In Experiment 3, animals receiving their daily injections of morphine were allowed to self-stimulate only at 3 h post-injection (when ICS facilitation is usually maximal), rather than at 1 h and 3 h post-injection. ICS facilitation was not observed, even with repeated testing. These data indicate that the facilitation of ICS by morphine is the outcome of a learned association between drug administration and the ICS procedure, rather than the invariable result of opiate receptor activation. Repeated exposure to morphine is required for the initial establishment of ICS enhancement, but the subsequent expression of this behavior is not directly related to opiate receptor activity.

Differential mechanisms in the acquisition and expression of heroin-induced place preference

“…However, Eikelboom and Stewart (1979) were unable to replicate this latter result. In addition, Hand and Franklin (1986) found that after several pairings of morphine and self-stimulation, the resuiting facilitation of this behavior was not consistently antagonized by naloxone, and hence unlikely to be opiate receptor mediated. The present data support their proposal that the reinforcing effects of opioids expressed in drug-free animals are mediated by an unidentified non-opioid mechanism, and argue strongly against the hypothesis that the conditioned effects of opioids are related to endogenous opioid activity.…”

“…This dissociation of mechanisms underlying acquisition and expression of drug effects on behavior is evident in a wide variety of pharmacological studies (Robertson et al 1982;Beninger and Hahn 1983;Hand and Franklin 1986;Snodgrass and Allen 1988), and suggests that the neural mechanisms underlying acquisition of certain behaviors are generally not recruited when the behavior is expressed. Nor may acquisition-related events even be involved in the retention of these behaviors over long periods of time.…”

Foster mother care but not prenatal morphine exposure enhances cocaine self‐administration in young adult male and female rats

“…It has also been shown that the most effective site to alter reward threshold with ICSS is in the medial forebrain bundle (MFB). Morphine (Hand & Franklin, 1986) and cocaine (Mague, Andersen, & Carlezon, 2005) administration potentiates ICSS responding in adult animals. Interestingly, our prenatal morphine exposure, on gestation Days 11-18, also enhances ICSS in the presence of a single 5 mg/kg cocaine injection in adult male rats (Vathy, 2002).…”

Role of Specific Synaptic Plasticity Interfering Peptides in the Expression of Morphine Induced Conditioned Place Preference in Mice

“…In addition, the dissociation of mechanisms underlying acquisition and expression of drug effects on behaviour is evident in a wide variety of pharmacological studies (Robertson et al, 1982;Beninger & Hahn 1983;Hand & Franklin 1986;Snodgrass & Allen 1988), and presumably the expression of morphine reward attributes to unidentified mechanisms rather than the traditional reward circuit.…”