Zavie W. Brown

The role of endorphins in stress: Evidence and speculations ☆

Several lines of evidence suggest that the endogenous opioid peptides endorphins may play a role in the defensive response of the organism to stress. The present paper summarizes these findings as well as evidence linking endorphins to the anterior pituitary polypeptide hormone adrenocorticotropin (ACTH). Evidence is presented that endorphins may function as trophic hormones in peripheral target organs such as the adrenal medulla and the pancreas. As such they may be part of the physiological mechanisms that mediate adrenaline and glucagon release in response to stress. Endorphins (enkephalins) are also suggested to play a role in the control of the pituitary gland during stress. In such capacity they may act as hormone-releasing or inhibiting factors. Finally, endorphins appear to play a role in the behavioral concomitants of stress. In such capacity endorphins are suggested to function as modulators of neural systems that mediate the elaboration and expression of the reactive/affective components of stress. Speculations on the mode of interaction between endorphins and ACTH in the global response to stress are discussed.

Intraventricular self-administration of acetaldehyde, but not ethanol, in naive laboratory rats

For 11 consecutive days, naive rats were maintained in operant chambers where they were given the opportunity to self-administer acetaldehyde (1,2, or 5% v/v), ethanol (2 or 10% v/v), or pH control solutions directly into the cerebral ventricles. Only the animals that had access to the 2 and 5% acetaldehyde solutions showed rates of lever pressing significantly higher than controls. It is suggested that acetaldehyde rather than ethanol itself may mediate the positive reinforcing effects of ethanol in the brain.

Simple flow-thru swivel for infusions into unrestrained animals.

Infusion of fluids into unrestrained animals requires the use of a flow-thru swivel. A method is described for the construction of a simple efficient swivel assembled from disposable plastic syringes and needles.

An investigation of the mechanisms of action of 5-hydroxytryptamine in the suppression of ethanol intake.

The effect of blockage of 5-hydroxytryptamine and norepinephrine uptake on voluntary ethanol consumption in rats was investigated. It was demonstrated that attenuation of ethanol intake occurred only as a result of treatment with specific 5-hydroxytryptamine uptake inhibitors. These results suggested that increasing the availability of central 5-hydroxytryptamine may in some way interfere with the positive reinforcing properties of ethanol. The second phase was designed to determine whether the attenuation of ethanol intake following blockade of 5-hydroxytryptamine uptake may be due to increased post-synaptic activity. Ethanol-preferring animals were pretreated with methergoline, a post-synaptic receptor blocker, followed by treatment with zimelidine, a 5-hydroxytryptamine uptake inhibitor. The results indicate that treatment with methergoline did not alter the zimelidine-induced attenuation of ethanol intake. Based on these results it is suggested that blockade of 5-hydroxytryptamine uptake produces an attenuation of ethanol intake but not as a result of increased post-synaptic activity.

Intraventricular self-administration of acetaldehyde and voluntary consumption of ethanol in rats.

For 11 consecutive days, naive male Wistar rats were given the opportunity to acquire an operant response for infusions of acetaldehyde or Ringers vehicle into the cerebral ventricles. The experimental group showed significantly higher rates of lever pressing than the control animals. Following the intraventricular self-administration period, all the animals in the acetaldehyde group were exposed to a free-choice between increasing concentrations of ethanol and water. The consumption of ethanol in the range of concentrations of 9 to 21% (v/v) was directly correlated to the previously established rates of self-administration of acetaldehyde. The results suggest that the central mechanisms mediating the reinforcing effects of acetaldehyde also subserve the pharmacologically reinforcing properties of ingested ethanol.

The effects of selective catecholamine depletions by 6-hydroxydopamine on ethanol preference in rats

Two groups of ethanol-drinking rats were subjected to differential treatments with 6-hydroxydopamine in order to selectively destroy norepinephrine- and dopamine-containing neurons in the brain. Animals with extensive depletions of norepinephrine and dopamine produced by treatment with pargyline prior to 6-hydroxydopamine infusions showed a significant attenuation of preference for alcohol. However, where norepinephrine neurons were protected from the neurotoxic effects of 6-hydroxydopamine by pretreatment with desmethylimipramine, the consequent effects on ethanol preference were not significant. It was suggested that catecholamines are involved in the mediation of ethanol self-administration with norepinephrine possibly playing the dominant role.

Lack of effect of dopamine receptor blockade on voluntary ethanol consumption in rats

Alcohol-drinking male Wistar rats consuming a 10% v/v ethanol solution presented in a free choice with water did not alter their intake of ethanol during 5 days of treatment with pimozide in doses of 0, 0.2, 0.4, and 0.6 mg/kg ip. These data suggest that the dopamine system is not involved in the mediation of the reinforcing effects of ethanol.

BODY PINCH INDUCES LONG LASTING CATALEPTIC LIKE IMMOBILITY IN MICE: BEHAVIORAL CHARACTERIZATION AND THE EFFECT OF NALOXONE

Abstract The present article reports that repeated exposure to brief pinches at the scruff in mice results in the development of long lasting cataleptic-like immobility. The response is robust, readily induced and involves changes in autonomic functions and pain sensitivity. The development of catalepsy and the concominant antinociception are blocked by naloxone pretreatment. In contrast, naloxone fails to suppress the pinch-induced catalepsy when administered after this behavior has already been established. Taken together, the findings offer a simple and most reliable model to study the neural mechanisms that mediate “naturally occurring”, stress- induced catalepsy.

Intraventricular self-administration of morphine in naive laboratory rats.

Male Wistar rats implanted with cannulae aimed at the left lateral cerebral ventricle were individually maintained in Skinner boxes for 11 consecutive days. Animals were neither predependent on morphine nor shaped to press the operant lever. Experimental animals (n=7) obtained intraventricular infusions of a 1% morphine HCl solution (2 μl per 5-s infusion) for each lever press while control animals (n=7) received only the vehicle. Four animals were yoked to experimental animals and received equivalent but non-contingent morphine HCl infusions. The mean number of lever presses per day for the experimental group was significantly higher than for the vehicle control or yoked control groups suggesting that naive rats will work for the positive reinforcing properties of morphine when it is infused centrally.

Possible involvement of acetaldehyde, norepinephrine and their tetrahydroisoquinoline derivatives in the regulation of ethanol self-administration

In this study, we examined the possible role of acetaldehyde in the mediation of the reinforcing properties of ethanol. We also examined the possible interaction of acetaldehyde and brain norepinephrine in this mediation. We found that rats will self-administer acetaldehyde delivered into the cerebral ventricles, and that this operant behaviour can be attenuated by injections of a dopamine-beta-hydroxylase inhibitor. The results are discussed in terms of a role for tetrahydroisoquinoline alkaloids in alcoholism.