The lateral habenula is a common target of cocaine and dexamethasone.
The lateral habenular nucleus (LHb) receives projections from areas rich in dopaminergic neurons and sends efferent fibers to these areas, suggesting that the LHb has a role in dopaminergic reward-related activity. The LHb is also implicated in multiple stress reactions, including responses to painful stimuli. However, it is unclear whether the LHb facilitates glucocorticoid/cocaine interactions by serving as a common target of both. In this study we investigated the effect of cocaine and dexamethasone (a synthesized glucocorticoid) on pain-related neurons (pain-excitatory and pain-inhibitory). Cocaine treatment effectively increased the firing rate of 89.7% of pain-excitatory neurons (cocaine-up response) and decreased the firing rate of 81.8% of pain-inhibitory neurons (cocaine-down response) in the LHb, suggesting that LHb neurons respond to cocaine via different mechanisms. Dexamethasone enhanced the firing rate of the cocaine-up neurons, while cocaine-down neurons were not influenced, indicating that both drugs may elicit an electrophysiological response at the same LHb neuron. Effects of either cocaine or dexamethasone alone, or both combined, on FOS expression in the LHb were observed via immunohistochemistry. Single administration of either cocaine or dexamethasone increased the number of FOS-positive neurons in the LHb. Pretreatment with dexamethasone and then cocaine markedly enhanced the number of FOS-positive neurons in the LHb relative to cocaine treatment alone, suggesting that stress and addictive drugs exert a synergistic effect on the LHb. We conclude that the LHb responds to cocaine via more than one mechanism and is a common target of both cocaine and the dexamethasone.
Physiology Department, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China.
Chun-Xiao
CX
Zhang
Hong
H
Zhang
Hai-Yan
HY
Xu
Ming-Xian
MX
Li
Shao
S
Wang
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology*; D019262:Habenula / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D016760:Proto-Oncogene Proteins c-fos; D003907:Dexamethasone; D003042:Cocaine
Cocaine; Dexamethasone; Extracellular firing; FOS expression; Glucocorticoid; Lateral habenular nucleus