Differential effects of conditioned and unconditioned stress on the neurotensin content of dopamine cell body groups of the ventral mesencephalon.
The findings of this study extend the observations of Deutch et al. who suggested that NT in the ventral mesencephalon may be involved in the environmentally elicited activation of selectively responsive populations of mesotelencephalic dopamine neurons. The unconditioned response of NT-LI to electric footshock was observed only at an intensity of 500 microA and only in the lateral subdivision of the VTA. The selective effect of footshock stress on the NT content of a specific cell body group of the ventral mesencephalon suggests that NT mechanisms in the lateral VTA may, in part, underlie the stress-induced activation of dopamine neurons that originate in the lateral VTA. However, it should be noted that populations of dopamine neurons are activated by footshock intensities less than 500 microA, while NT concentrations of mesencephalic dopamine cell body groups are not altered by these shock intensities. The disparity weakens the possibility of a role for NT in the stress-induced activation of brain dopamine neurons unless NT mechanisms may be involved in transducing the effects of higher intensity stressors versus low intensity stressors. However, it should be noted that changes in the concentration of NT-LI represent an endpoint of unknown sensitivity and functional significance and best serve as an initial approximation of the effects of a manipulation on NT-containing neurons. It is plausible that NT mechanisms in the ventral mesencephalon may act in concert with other neuropeptides such as substance P and Met-enkephalin to transduce the effects of stressors on alterations in the activity of mesotelencephalic dopamine neurons that originate in the ventral mesencephalon. An examination of the effects of footshock stress on the content of prepro-NT mRNA in the dopamine cell body groups of the ventral mesencephalon would be of interest in assessing whether stress enhances NT gene expression or alters the characteristics of release of this neuropeptide in the ventral mesencephalon. Lacking NT receptor antagonists, it would also be of interest to determine the effects of the passive immunoneutralization of NT in the ventral mesencephalon on footshock-induced increases in the biochemically estimated activity of mesotelencephalic dopamine neurons to better understand the involvement of NT as a transducer of the effects of stress on dopamine neuronal activity. The distinct topography of conditioned versus unconditioned stress on the concentration of NT-LI in the dopamine cell body groups of the ventral mesencephalon suggests that NT may be involved in the differential activation of distinct dopamine neuronal populations by these different stressors.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
C D
CD
Kilts
M L
ML
Coco
T D
TD
Ely
G
G
Bissette
C B
CB
Nemeroff
D000818:Animals; D001921:Brain / Q000378:metabolism; D003213:Conditioning, Psychological; D003975:Diazepam / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D008297:Male; D009474:Neurons / Q000378:metabolism; D009496:Neurotensin / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*; D013681:Tegmentum Mesencephali / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D009496:Neurotensin; D014446:Tyrosine 3-Monooxygenase; D003975:Diazepam; D004298:Dopamine