3-acetylpyridine (3-AP) is a neurotoxin that is known to mainly affect the inferior olivary nucleus (ION) in the brain stem. It targets the ascending neurons of IO that climb into the Purkinje cells of the cerebellum (Balaban, 1985, Fowler et al., 2005). Studies show that the concentration of glutamate and aspartate, a probable candidate that plays a neurotransmitter role in the IO climbing fibers(Guidotti, Biggio et al. 1975, Nadi et al., 1977) decreases in the cerebellum of the mice treated with 3-AP(Butterworth, Hamel et al. 1978, McBride, Rea et al. 1978, Rea, McBride et al. 1980). This results in ataxia in which both balance and gait are impaired (Wecker, Marrero-Rosado et al. 2017). Although this is known to be the main effect of 3-AP on the central nervous system (CNS), some studies suggest that this toxicity does not completely spare other regions of the brain. According to studies, the rats receiving systemic administration of 3-AP experienced serotonin (5-HT) related changes in their voluntary movements followed by a decreased level of 5-HT immunoreactivity in the neurons of their nucleus raphe obscurus, positioned midline along the whole brainstem, compared to the control group (Wieland, Kreider et al. 1990).

It should be noted that the recent finding that 3-AP toxicity is reduced by free radical scavengers after systemic treatment in vivo raises the possibility that oxidative stress potentially contributes to 3-AP toxicity (Alyu and Dikmen 2017). Free radicals may play a dual role. Reactive oxygen species, for example, can directly harm cellular organelles by oxidizing proteins, lipids, and DNA. On the other hand, a rise in free radicals may be a precursory event that could signal the beginning of neuronal death. Numerous neurodegenerative illnesses, including Huntington's and Alzheimer's, have been linked to apoptosis (Portera-Cailliau et al., 1995, McElroy et al., 2017, Novak et al., 2022).

It has been reported that the administration of 3-AP to rats degenerates the dopamine innervation of the striatum(Deutsch, Elsworth et al. 1990). Studies on the neurotoxic effect of 3-AP on the mesencephalic dopamine system in mice using the tyrosine hydroxylase (TH) immunohistochemistry method have revealed that the systemic injection of 3-AP leads to a huge reduction in TH-immunoreactive nigrostriatal neurons(Takada and Kono 1993). These studies have shown the effect of 3-AP on olivocerebellar and nigrostriatal neurons to match the neuropathological feature of olivopontocerebellar atrophy-associated parkinsonism. Therefore 3-AP induced rats are used in studies as a model for parkinsonism features. Whereas, past studies suggest that the neurotoxic effect of 3-AP is not specific and can have several effects on other regions of the CNS. Hence, the main goal of this study is to discover whether other regions of the CNS, such as the hippocampus and the striatum, are affected by the toxicity of 3-AP.