The etiology of Parkinson’s disease is multifactorial. Genetic, environmental and inflammatory processes are involved. Recently, it has been shown that anti-inflammatories reduce lesion volume after postnatal excitotoxic damage (Acarin et al. 2002). If inflammatory response is related to the progression of secondary neuronal damage, pretreatment with anti-inflammatories may improve some Parkinson’s disease (PD) symptoms. PD is characterized by a severe decrease of brain dopamine (DA) and brain DA dysfunction impairs intracranial self-stimulation (ICSS). The objective of this research was to assess if two anti-inflammatories (indomethacin and chloroquine) protect against experimental PD produced by 6-hydroxydopamine (6-OHDA) lesions.

Thirty rats were divided into four groups: a control group (sham operated, n = 10), which received vehicle injection into right striatum; a lesion group (n = 9) which received 6-OHDA injection into right striatum; an indomethacin group, which after 5 days of treatment with indomethacin (2 mg in DMSO per kg body weight) was lesioned with 6-OHDA; and a fourth group, which received 5 days of chloroquine (5 mg kg^-1 b.w.) before 6-OHDA lesion. Rats were anaesthetized with Equithensin (2 ml (kg body weight)^-1 S.C. Co-ordinates of lesion were: 0 mm AP, 3 mm lateral and 5 mm deep. On the last day of pretreatment, they were anaesthetized with equithensin and 4 µl of saline or 6-OHDA (32 µg/4 µl of saline) was injected stereotaxically. Two months after the lesion, rats were implanted bilaterally with monopolar electrodes into the medial prefrontal cortex. Then, they were trained to press a bar to receive electrical ICSS. All of them learnt ICSS behaviour in 1 week, and current intensity was manipulated in order to obtain the lowest intensity which would generate an optimal rate of response for a particular animal. This current intensity was used to establish a reliable ICSS performance. Spontaneous motor activity was also measured as a control. Animals were killed humanely.

The lesion group showed a significantly lower ICSS rate than groups with anti-inflammatory pretreatment and 6-OHDA lesions, which, in turn, showed a lower rate than control group. Significant differences in spontaneous motor activity were not found. In conclusion, the administration of indomethacin and chloroquine protected against 6-OHDA effects on prefrontal self-stimulation.

Junta de Andalucia through PAI CTS-438 and PAI CVI-221 (Acciones Coordinadas) supported this work.