6-HYDROXYDOPAMINE TREATMENT OF NEONATAL RATS .2. EFFECTS ON THE DEVELOPMENT OF THE HINDLIMB FLEXOR REFLEX

The flexor reflex (FR) of the hindlimb was measured in rats at various ages between postnatal days (PND) 12-45, in vehicle-treated control rats and in rats treated with 6-hydroxydopamine (6-OHDA) (100 mg/kg, i.p.) on the first and second days after birth. The hindlimb FR was elicited by graded electrical stimulation of the footpad (0.1-2.0 mA) and quantified by the amplitude of the flexion in grams. The half maximal FR response was evoked by 1.2 mA and was 2-3 g in animals at PND 12-17 and 9-10 g in animals on PND 30 and 45. A similar age dependency was evident in the maximum hindlimb FR evoked by 2.0 mA; the maximum FR was 4.7 +/- 0.5 g on PND 12 and 24 +/- 2 g on PND 45. In rats treated with 6-OHDA, the strength of the FR was similar to that of the controls up to PND 15. However, the FR was increased 25% by PND 17 and 200% by PND 45 in the 6-OHDA-treated animals, versus controls. Pretreatment with clonidine (100 mug/kg, i.p.), which activates alpha1 receptors under the current experimental conditions, did not enhance the FR in control animals. However clonidine pretreatment caused an increase of 400-800% in the FR in the 6-OHDA-treated animals at PND 15 and beyond. Our companion paper demonstrated that as early as PND 5, there was a significant increase (P < 0.05) in alpha1 receptors in the spinal cord of 6-OHDA-treated animals, versus the controls34. The temporal disparity between increased alpha1 receptors and the increased FR in 6-OHDA-treated animals suggests that factors other than increased alpha1 receptors might be involved in the enhancement of the FR.