Previously we found that intra-ventral tegmental injections of the cholinergic agonist carbachol produce a rewarding effect; rats self-administer carbachol at a relatively fast rate directly into the ventral tegmental area (VTA). We sought to determine brain regions that are activated by intra-VTA carbachol using the immunohistochemical technique for detection of c-Fos protein. Nine brain regions were examined to determine the number of neurons expressing c-Fos immunoreactivity in 13 rats: 5 rats received 500 pmol carbachol into the posterior VTA, 5 received the carbachol solution into the region 1 mm dorsal to the VTA, and 3 received vehicle (0.5 ?l) into the VTA. We observed notable increase (>400%) of c-Fos expression in four brain areas after intra-VTA carbachol injections: retrosplenial granular (posterior cingulate) cortex (500%), supramammillary nucleus (700%), anterior VTA (400%), and interpeduncular nucleus (1700%). Furthermore, locomotor distance during the first 10 min just after microinjections was significantly correlated with c-Fos expression in the retrosplenial granular cortex (0.71), supramammillary nucleus (0.70), and anterior VTA (0.73), but not the posterior VTA (0.12; injection site) or interpeduncular nucleus (0.45; most carbachol-sensitive site with respect to % increase from vehicle baseline). The high correlation coefficient between carbachol-induced c-Fos activation and locomotor activation suggest that in particular, retrosplenial granular cortex, supramammillary nucleus, and anterior VTA play an important role in intra-VTA carbachol induced locomotion, and possibly reward. Whether or not carbachol is exciting or inhibiting those neurons that initiate the behavioral effects remains to be determined.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000446-03
Application #
6830666
Study Section
(BNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2003
Total Cost
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code