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Herpes virus-mediated preproenkephalin gene transfer in the ventral striatum mimics behavioral changes produced by olfactory bulbectomy in rats.
- Source :
-
Brain research [Brain Res] 2003 Oct 24; Vol. 988 (1-2), pp. 43-55. - Publication Year :
- 2003
-
Abstract
- The syndrome of behavioral, physiological, and neurochemical changes caused by ablation of the olfactory bulbs (OBX) in rats serves as a reliable and well-validated model of depression. Previous experiments have demonstrated that OBX leads to increased expression of the preproenkephalin (ENK) gene in the olfactory tubercle (OT) portion of the ventral striatum in rats. The aim of the present experiments was to investigate the role of OBX-induced ENK overexpression in the OT in the behavioral abnormalities exhibited by bulbectomized rats. A recombinant herpes virus carrying human preproENK cDNA was used to manipulate ENK gene expression in the OT of bulbectomized and sham-operated rats. Motivational deficits were assessed by the sucrose preference test, and 'agitation-like' behaviors were measured with the novel open field and footshock-induced freezing tests. ENK gene transfer in sham-operated rats mimicked some of the effects of OBX; it decreased freezing behavior in response to mild footshock and produced behavioral activation in the open field. In another experiment, virally mediated ENK gene transfer into the OT of intact rats decreased footshock-induced freezing, and this effect was reversed by naltrexone administration. PreproENK gene transfer into the OT did not produce analgesic effects in the tail-flick test. No effects on freezing behavior were observed following preproENK gene transfer into the frontal cortex. An additional experiment revealed that naltrexone administration attenuated the OBX-induced abnormality in freezing behavior. The results indicate that overexpression of the preproENK gene in the ventral striatum may mediate the 'agitation-like' behavior exhibited by bulbectomized rats.
- Subjects :
- Animals
Basal Ganglia metabolism
DNA, Complementary
Enkephalins metabolism
Male
Naltrexone pharmacology
Narcotic Antagonists pharmacology
Protein Precursors metabolism
Psychomotor Agitation drug therapy
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation drug effects
Behavior, Animal
Enkephalins genetics
Gene Transfer Techniques
Herpesviridae
Olfactory Bulb surgery
Olfactory Pathways metabolism
Protein Precursors genetics
Psychomotor Agitation metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-8993
- Volume :
- 988
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 14519525
- Full Text :
- https://doi.org/10.1016/s0006-8993(03)03337-7