TMT, a predator odor, elevates mesoprefrontal dopamine metabolic activity and disrupts short-term working memory in the rat.
Working memory has been proposed to require the proper functioning of the medial prefrontal cortex and its dopaminergic innervation. The dopaminergic input to the medial prefrontal cortex has been demonstrated to be sensitive to physical and psychological stress. In this report, we demonstrate that a brief exposure to 2, 5-dihydro-2,4,5-trimethylthiazoline (TMT), an odor derived from a predator of the rat, the fox, resulted in elevated dopamine metabolism in the medial prefrontal cortex and elevated serum corticosterone. We tested the effects of this olfactory stress on working memory using a spontaneous, delayed, non-matching-to-sample task using object recognition methods. Rats were exposed to one set of objects and, after a delay of 1, 15 or 60 min, later demonstrated a robust working memory of the familiar object compared to a novel object. When rats were exposed to TMT during the 15-min delay, working memory was disrupted without altering exploratory behavior. We conclude from these studies that (1) TMT selectively activates mesoprefrontal dopamine neurons, (2) TMT exposure can disrupt working memory and (3) this disruption in working memory is not due to an overall suppression of exploratory behavior but may involve altered mesoprefrontal dopaminergic activity.
Morrow
B A
BA
Department of Pharmacology, Laboratory of Neuropsychopharmacology, Yale University School of Medicine, New Haven, CT 06520-8066, USA. bret.morrow@yale.edu
Roth
R H
RH
Elsworth
J D
JD
D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005239:Fear / Q000187:drug effects / Q000502:physiology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009812:Odorants; D009833:Olfactory Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000139:chemically induced / Q000503:physiopathology*; D013844:Thiazoles / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
C411827:2,5-dihydro-2,4,5-trimethylthiazoline; D013844:Thiazoles; D004298:Dopamine; D003345:Corticosterone