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6-Hydroxydopamine treatment of neonatal rats. II. Effects on the development of the hindlimb flexor reflex
1Department of Anesthesiology, University of Texas Health Science Center, San Antonio 78284-7838.
Insights
Neonatal 6-hydroxydopamine (6-OHDA) treatment in rats significantly enhances hindlimb flexor reflex (FR) development and alpha-1 receptor sensitivity later in life. This suggests a crucial role for early dopaminergic system development in regulating spinal reflexes.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- The flexor reflex (FR) is a fundamental spinal cord-mediated motor response.
- Developmental changes in spinal cord circuitry influence reflex excitability.
- The role of early life neurochemical insults on reflex maturation is not fully understood.
Purpose of the Study:
- To investigate the long-term effects of neonatal 6-hydroxydopamine (6-OHDA) administration on the developmental trajectory of the hindlimb flexor reflex (FR) in rats.
- To examine the influence of 6-OHDA-induced neurochemical changes on the sensitivity of the FR to alpha-1 adrenergic receptor activation.
Main Methods:
- Hindlimb FR was measured in rats aged postnatal days (PND) 12-45.
- Rats were treated neonatally with 6-hydroxydopamine (6-OHDA) or vehicle.
- FR was elicited via electrical footpad stimulation and quantified by flexion amplitude; clonidine was used to assess alpha-1 receptor function.
Main Results:
- Neonatal 6-OHDA treatment did not alter FR up to PND 15 but significantly increased FR amplitude by PND 17 (25%) and PND 45 (200%) compared to controls.
- Clonidine significantly enhanced FR in 6-OHDA-treated rats (400-800% increase) from PND 15 onwards, but not in controls.
- Increased spinal cord alpha-1 receptors were observed in 6-OHDA-treated rats as early as PND 5.
Conclusions:
- Neonatal dopaminergic denervation via 6-OHDA leads to a delayed but substantial potentiation of the hindlimb flexor reflex during postnatal development.
- This potentiation is associated with enhanced alpha-1 adrenergic receptor-mediated modulation of spinal reflex pathways.
- Early life alterations in the dopaminergic system can profoundly impact the maturation and regulation of spinal cord motor circuits.
Abstract:
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 micrograms/kg, i.p.), which activates alpha 1 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 alpha 1 receptors in the spinal cord of 6-OHDA-treated animals, versus the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
