Antidepressant treatment prevents chronic unpredictable mild stress-induced anhedonia as assessed by ventral tegmentum self-stimulation behavior in rats.
The effect of chronic unpredictable mild stress on sensitivity to reward was evaluated using the brain self-stimulation procedure. Rats were allowed to electrically self-stimulate the ventral tegmental area, one of the main cerebral structures subserving positive reinforcement. Stimulation thresholds (frequency of stimuli) for self-stimulation responses were determined prior to, during, and following a 19-day period of exposure to a variety of mild unpredictable stressors. Stimulation threshold was increased in stressed rats, suggesting a decrease in the rewarding properties of brain stimulation. This deficit became evident after about 1 week of mild stress, lasted throughout the stress period, and progressively diminished following termination of the stress regime. In stressed rats concomitantly treated with the tricyclic antidepressant desipramine (5 mg/kg b.i.d.), no stress-induced increase in self-stimulation threshold was observed. However, desipramine did not modify self-stimulation threshold in non-stressed animals. Thus, the increased threshold for brain self-stimulation produced by a period of chronic unpredictable mild stress can be completely prevented by concomitant antidepressant treatment and may provide an heuristic animal model of depression.
Moreau
J L
JL
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Jenck
F
F
Martin
J R
JR
Mortas
P
P
Haefely
W E
WE
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004566:Electrodes; D008297:Male; D051381:Rats; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*; D013315:Stress, Psychological / Q000523:psychology*; D013681:Tegmentum Mesencephali / Q000033:anatomy & histology / Q000502:physiology*
D000928:Antidepressive Agents