The effects of footshock stress on regional brain dopamine metabolism and pituitary β-endorphin release in rats previously sensitized to amphetamine

Abstract

The repeated intermittent administration of amphetamine (AMP) produces an enduring enhancement in the response of dopamine (DA) systems in the brain to a subsequent "challenge" with amphetamine. However, former amphetamine addicts are not only hypersensitive to amphetamine, but also to "physical or psychological stress". This suggests that sensitization to amphetamine may change the response of DA neurons in brain to subsequent stress. To explore this idea, the effects of footshock stress on regional metabolism of DA in brain, and on the concentrations of plasma beta-endorphin and N-acetylated beta-endorphin, were studied in rats previously exposed to amphetamine or saline. It was found that: Prior treatment with amphetamine produced enduring (at least 7 days) changes in the dopaminergic response to footshock in the medial frontal cortex, hypothalamus, dorsolateral striatum and nucleus accumbens. Generally, rats pretreated with amphetamine showed a greater initial reduction in concentrations of DA in response to footshock, and a greater elevation in concentrations of metabolites of DA and/or metabolite/transmitter ratios, compared to nonhandled control rats. In some regions of the brain repeated injections of saline produced changes in the response to subsequent footshock that were comparable to those produced by amphetamine. Prior treatment with amphetamine enhanced the release of beta-endorphin and N-acetylated beta-endorphin from the pituitary elicited by footshock stress. It is concluded that repeated intermittent treatment with amphetamine or stress (injections of saline) produce enduring changes in the response of DA neurons and the pituitary to subsequent stress. These changes may be responsible for the hypersensitivity to stress reported in former amphetamine addicts, and in rats previously sensitized to amphetamine.

Neurobiological basis of relapse prediction in stimulant-induced psychosis and schizophrenia: the role of sensitization

“…This stress sensitization may help explain why psychosis only recurs in subjects with a history of AMP psychosis following exposure to stress. 9 Previous exposure to stressful stimuli induces noradrenergic hyperreactivity to subsequent mild stress. 10 Stress-induced noradrenergic hyperactivity may be a precipitating factor in stressrelated psychiatric disorders.…”

“…The present findings on plasma monoamine metabolite levels suggest that increased noradrenergic activity be related to the occurrence of flashbacks. Considering that stressful stimuli induce noradrenergic hyperreactivity to subsequent stress, 10 and that AMP induced enduring sensitization to stress, 9,15 threatening experiences together with MAP use may have increased sensitivity to subsequent exposure to similar but less severe situations, so that heightened NE release may have been elicited in response to a mild fear of other people. It has been documented that 3-MT levels in the rat brain serve as a sensitive index of dopamine release.…”

“…20 AMP-induced sensitization to stress in dopaminergic systems may be related to the enduring hypersensitivity to the psychotogenic effects of stress in spontaneous recurrences of AMP psychosis. 9 Therefore, a mild fear of other people may have elicited memories of MAP psychosis related to threatening experiences through increased sensitivity to stress associated with a predominance of noradrenergic over dopaminergic hyperactivity. As a result the flashbacks may have been triggered.…”

Effects of Cortical Serotonin Depletion Induced by 3,4-Methylenedioxymethamphetamine (MDMA) on Behavior, Before and After Additional Cholinergic Blockade

“…The samples were homogenized and centrifuged at 1500g for 4 minutes. The supernatant was flltered and assayed by HPLC and electrochemical de tection using procedures similar to those described pre viously (Robinson et al 1987).…”

Evaluation of the Effects of Restraint and Footshock Stress on Small Intestinal Motility by an Improved Method Using a Radionuclide, <SUP>51</SUP>Cr, in the Rat

“…It has been well known that both footshock stress and restraint stress elevate the plasma concentration of catecholamines. [19][20][21] Rossier et al and Robinson et al have also reported that footshock stress significantly elevates the plasma concentration of b-endorphin, 22,23) whereas Williams et al have reported that the restraint stress only slightly elevates plasma b-endorphin concentration. 13) We also observed that the increase in plasma bendorphin after footshock stress was higher than that after restraint stress (data not shown).…”