Abstracts

RATIONALE: We have previously reported that kindling can occur following the repeated administration of nicotine (1). In the present study we investigated this model further by examining the neuronal activity following a seizure, using c-Fos expression as a marker of neuronal activity. Furthermore, we compared the expression pattern of the nicotine kindling model with that of the PTZ kindling (2) and a cocaine kindling model (3).
METHODS: Kindling was induced in male NMRI mice by injection of either cocaine (48 mg/kg) every day for 5 days, PTZ (37 mg/kg) every other weekday for 3 weeks, or nicotine (2.3 mg/kg) every weekday for 2 weeks. Mice were transcardially perfused with heparinised saline on the last experimental day and c-Fos expression patterns were determined using standard immunohistochemistry methods.
RESULTS: PTZ-induced seizures increased fos-expression in motor cortex (MC), paraventricular thalamic nucleus (PV), medial habenula (MHb), pirifrom cortex (PC), entorhinal cortex (EC), amygdala (AM) and to some extent in the hippocampus. Cocaine-induced seizures generally increased fos-expression in MC, caudate putamen, nucleus accumbens, PV, lateral habenula (LHb), EC, PC, substantia nigra pars compacta (SNC) and in the AM. Nicotine-induced seizures increased fos-expression in MC, nucleus accumbens (shell), PV, MHb, EC, SNC and peripeduncular nucleus. In addition, a difference in activity pattern between seizures in na[iuml]ve and kindled animals was observed in the nicotine kindling experiment with a decreased expression in the MHb and an increased expression in the SNC. A difference was also seen in the cocaine models with increased expression in the LHb in the cocaine kindling mice. There were no observable differences were seen in expression patterns between PTZ kindled and non-kindled mice.
CONCLUSIONS: In conclusion, nicotine seizures seemed to originate partly in the hindbrain and spread to the forebrain - as well as involve the MHb. C-fos induced by PTZ seizures was mainly restricted to the limbic system. Cocaine-induced seizures seemed to involve the limbic system, structures in the basal ganglia and possibly also the LHb. Data in the present study also suggests that the MHb and SNC may undergo functional changes following nicotine kindling.
1. Bastlund J.F, Watson W.P., Sanchez C. (2002) Br J Pharmacol Suppl, in press:
2. Mason CR, Cooper RM (1972). Epilepsia;13:663-74.
3. Post RM. Et al., (1988). Adv Exp Med Biol.;245:441-63.
[Supported by: H.Lundbeck A/S]; (Disclosure: Salary - H.Lundbeck A/S)