Philippine E-Journals

The Behavioural Pharmacology of the NAALADase Inhibitor: Its Effect on Cataleptic and Hemi-Parkinsonian Rats

Francis Rodriguez Bambi Co

Discipline: Psychology

 

Abstract:

The grid and bar test for catalepsy was performed on experimental rats to determine whether or not the NAALADase (N-acetylated-alpha-linked-acidic-dipeptidase) inhibitor GPI5OOO could be a potential pharmacological agent for the treatment of Parkinson's Disease (PO). The results were compared with those of trials ran to test the inhibitor's effect on rotational behaviour after unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the medial forebrain bundle (MFB), the outcome of which corroborated the catalepsy test. To surmise, GP15000 exhibited a moderate cataleptogenic effect both on the gird and the bar, and when combined with haloperidol, significantly potentiated the neuroleptic's cataleptogenic activity. Furthermore, GPI5OOO did not block haloperidol-induced sensitization to catalepsy, measured by the progressive increase in the latency of limb descent on the grid and in the latency of limb withdrawal on the bar. Data on rotational behaviour indicated that GP15000 did not induce rotation on its own, but increased apomorphine induced contralesional rotation. It has been established by previous studies that GPI5000 facilitates increase in the neuropeptide N-acetly-aspartylglutamate (NAAG). NAAG may exert an NMDA-independent mechanism of suppressing DA release. NAAG also modifies GABAAreceptor subtype expression, and enhances GABAergic activity. Based on these findings, the potential use of GP15000 as an anti-Parkinsonian agent is rather doubtful, but it opens a window for furthering research on its potential for the treatment of dysfunctions associated with hyperactivity of GLU and/orDA, e.g. addiction and schizophrenia.