J. Michael Walker

Effect of naloxone on analgesia induced by food deprivation

Abstract Naloxone (4 mg/kg) or saline was administered to animals under food deprived and non-deprived conditions prior to testing pain sensitivity in the tail flick test. Food deprived animals exhibited significantly elevated latencies in comparison to latencies observed under non-deprived conditions. This analgesia was diminished by treatment with the opiate receptor antagonist, naloxone. These findings suggest that analgesia induced by food deprivation is mediated in part by opiate receptor systems.

Effect of opiate receptor blockade on pain sensitivity in the rat

Blockade of opiate receptors by naloxone (2 mg/kg) was found to produce a significant increase in pain sensitivity as measured by the tail-flick test. This finding supports the view that endogenous opiate systems may play a role in the modulation of pain sensitivity. Naloxone, however, was found to have no effect on pain responsiveness as measured by tail-pinch. These findings, together with additional reports, suggest that endogenous opiate systems may exert differential actions on different sensory modalities.

Increase in rat striatal extracellular dopamine and vacous chewing produced by two σ receptor ligands

The present studies were carried out to analyze the neurochemical and behavioral effects of peripheral sigma ligand administration in the rat. Based upon previous studies which showed an increase in turning behavior following unilateral intranigral administration of sigma ligands, we determined the effects of two sigma ligands, 1,3-di-o-tolylguanidine (DTG) and (+)-pentazocine, on extracellular dopamine levels in the rat striatum. Dopamine levels were monitored via microdialysis in awake freely moving animals following i.p. injection of the ligands. Both DTG (1 and 3 mg/kg) and (+)-pentazocine (10 mg/kg) produced a significant (30-50%) increase in extracellular dopamine. Given the relatively high concentration of sigma receptors in brain nuclei involved in facial and mouth movements, we have also determined the effects of the two sigma ligands on facial movements. Both ligands produced a significant increase in vacuous chewing movements, suggesting that studies on the consequences of sigma receptor activation may have relevance to animal models of human dystonia and/or dyskinesia.

Blockade of endogenous opiates reduces activity in the rat

Naloxone (2 mg/kg, SC) was found to result in a substantial and significant reduction in general activity levels in the rat (90--120 days old). This effect was seen both under baseline conditions and after stress manipulations which would be expected to result in elevated levels of endogenous opiate peptides. Thus, under baseline conditions general activity was reduced to less than half of the saline control value thirty min after injection. Similarly, a reduction was seen after stress induced by a 30 min swim. While naloxone may have some non-opiate effects, these results support the view that endogenous opiate systems may play an important activational role in behavioral regulation, under baseline conditions and conditions of stress.

Endorphin analogs with potent and long-lasting analgesic effects

The analgesic effects of intracerebroventricular administration of alpha, gamma, and beta-endorphin and their D-Ala2-analogs were examined in the rat using the tail-flick test. Analgesia was produced by all substances. The actions of D-Ala2-alpha and -beta-endorphin were considerably greater than the parent forms, whereas D-Ala2-gamma-endorphin was approximately equivalent to the parent compound. The marked analgesia was dose dependent and prolonged for all analogs. Since these effects were reversed by the opiate antagonist naloxone, it was concluded that opiate receptors mediate the action of these analogs. It is suggested that these analogs may be useful in behavioral tests when a longer duration of action is desirable.

Induction of analgesia by central administration of ORG 2766, an analog of ACTH4-9

Dose-dependent analgesia was produced by microinjection of ORG 2766 into the periaqueductal gray (PAG). This analgesia was found to be potent and long-lasting and occurred at doses which were equimolar to those necessary for morphine analgesia. The same doses failed to produce analgesia by the cerebroventricular route, suggesting that the PAG was the site of action of this effect. Naloxone failed to reduce the analgesia and morphine tolerant did not diminish the effect significantly. Additionally, ORG 2766 at concentrations up to 10 micrometer failed to inhibit binding of [3H]naloxone to brain opiate receptors in vitro. These results suggest a non-opiate mechanism of action and are discussed in terms of a proposed alpha-MSH or ACTH receptor.

Systemic administration of endorphins selectively alters open field behavior of rats

Abstract A single intraperitoneal injection of 100 μg of α, γ, and β-endorphin or their [D-Ala 2 ] analog influenced the behaviors of male rats tested in the open field. Beta-endorphin significantly increased grooming behavior whereas [D-Ala 2 ]-α-endorphin appeared to enhance sexual arousal. Both γ-endorphin and [D-Ala 2 ]-γ-endorphin affected separate measures indicative of heightened emotionality. It appears that systemic injections of these fragments of β-LPH are capable of modulating behaviors unrelated to analgesia. Furthermore, the selective effects of these peptides suggest the possibility that each may be coded to act upon receptor sites in a differential manner resulting in separate and distinct patterns of behavioral alterations.

Effects of nicotinic and muscarinic compounds on biting attack in the cat

Predatory-like biting attack on a rat, as well as hissing, growling, and other threat behaviors, could be induced in normally non-aggressive cats by systemic administration of the muscarinic agonist, arecoline (7-12 mg/kg). In contrast to arecoline, nicotine was found to suppress aggressive behaviors. Systemic administration of nicotine (0.5 mg/kg) prior to arecoline injection resulted in a significant reduction in elicited attack and threat behaviors. Furthermore, nicotine (0.075-0.500 mg/kg) was found to produce a dose-dependent suppression of natural predatory behavior as well. This nicotine-produced suppression of attack did not appear to be due to the induction of general malaise, since attack suppression could be seen in the absence of general behavioral inhibition, and doses of nicotine resulting in complete suppression of attack had little effect on food intake. Results indicate that muscarinic and nicotinic compounds can exert antagonistic control over some types of aggressive behaviors.

Methods for rapid quantification of brain autoradiographs

Apparatus and methods are described for rapid semiautomatic quantification of silver grain densities in brain autoradiographs. The output voltage of a photodiode used with dark-field oil microscopy reflects the amount of label in a 35 by 35 square micra area of brain tissue. Apparatus are described for monitoring the movement of a microscope stage, and a microprocessor interface is described that provides hard-copy and paper-tape output of grain densities for later processing.

A simple IC pulse-pair stimulator

The present paper describes a simple and relatively inexpensive brain stimulator circuit for generating trains of conditioning (C) and test (T) pulse pairs for refractory period and excitability cycle analyses. G and T outputs are constant-current monophasic cathodal pulses of adjustable frequency, duration, amplitude, and delay. C and T pulses can be controlled manually or through logic programming and can be fed out the same or separate channels. The stimulator can be operated on either ac or dc supplies and, when battery operated, features a high degree of stimulus isolation.