DISCRIMINABLE EXCITOTOXIC EFFECTS OF IBOTENIC ACID, AMPA, NMDA AND QUINOLINIC ACID IN THE RAT LATERODORSAL TEGMENTAL NUCLEUS

Excitotoxins are valuable tools in neuroscience research as they can h elp us to discover the extent to which certain neurones are necessary for different types of behaviour. They have distinctive neurotoxic eff ects depending on where they are infused, and this study was conducted to delineate the neurotoxic profiles of excitotoxins in the laterodor sal tegmental nucleus (LDTg). Two 0.1 mu l infusions of 0.1 M ibotenat e, 0.1 M quinolinate, 0.04-0.1 M NMDA, or 0.05-0.015 M AMPA, were made unilaterally into the LDTg under either pentobarbitone or Avertin ana esthesia. The injection needle was oriented at an angle of 24 degrees from vertical in the mediolateral plane. After 23-27 days, sections th rough the mesopontine tegmentum were processed using standard histolog ical procedures for NADPH-diaphorase histochemistry, tyrosine hydroxyl ase or 5-hydroxytryptamine immunohistochemistry, and Cresyl violet. Le sions were assessed in terms of the size of the damaged area (identifi ed by reactive gliosis), the extent of cholinergic cell loss in the me sopontine tegmentum (by counting NADPH-diaphorase-positive neurones), and neuronal loss induced in the locus coeruleus and dorsal raphe nucl eus. Ibotenate induced compact lesions in the LDTg (more than 80% chol inergic loss) and did little damage to the locus coeruleus and dorsal raphe nucleus. Quinolinate and low doses of AMPA and NMDA made very sm all lesions with less than 35% cholinergic loss, while at higher doses , AMPA and NMDA induced large areas of reactive gliosis but killed onl y a proportion of the cholinergic neurones. AMPA appeared to have a pa rticular affinity for noradrenergic neurones in the locus coeruleus, w ith the 0.015 M dose injected into the LDTg typically destroying the m ajority of these neurones. The results are discussed in the context of what is known about the mechanisms of excitotoxins and the glutamate receptor profile of mesopontine neurones.