Infusion of a monoamine oxidase inhibitor into the locus coeruleus can prevent stress-induced behavioral depression

Abstract

Behavioral depression produced by exposing animals to a Stressor that they cannot control (uncontrollable shock) was reversed by infusion of the monoamine oxidase (MAO) inhibitor pargyline into the locus coeruleus (LC) region of the brain stem. Following exposure to uncontrollable shock, rats were infused through bilateral cannulas implanted in the LC region with either pargyline or vehicle. At 110 min after infusion, animals were tested for behavioral activity in a swim tank. Immediately following the behavioral test, animals were sacrificed for determination of the monoamines [norepinephrine (NE), dopamine (DA), serotonin (5-HT)], as well as 5-hydroxy-indoleacetic acid (5-HIAA) in various brain regions. The results showed that animals exposed to uncontrollable shock and then infused with vehicle exhibited significantly less activity in the swim test than animals not exposed to shock and similarly infused with vehicle; thus, the usual behavioral depression following exposure to uncontrollable shock was observed. On the other hand, shocked animals infused with pargyline did not show reduced activity in the swim test. Unshocked animals infused with pargyline showed no more activity than did shocked animals infused with pargyline or unshocked animals infused with vehicle, which demonstrated that the infusion of pargyline into shocked animals did not eliminate the shock-induced depression of activity simply by generally stimulating motor activity. Measurement of the concentration of NE, DA, 5-HT, and 5-HIAA present in seven brain regions at the conclusion of the swim test showed that pargyline infusion into the LC eliminated the large depletion of NE in the LC that is normally observed after exposure to uncontrollable shock while having no effect on NE levels in the other brain regions examined. The level of 5-HT in the LC was also raised by infusion of pargyline into the LC, but again, there was no effect of pargyline infusion on 5-HT levels in any of the other brain regions. In conclusion, infusion of pargyline into the LC region of the brain eliminated both the large depletion of NE in the LC region and the behavioral depression that otherwise results from exposure of animals to uncontrollable shock.