The proposed research will use a new paradigm, drug-elicited air- stepping, to study the development of locomotion and its neuropharmacological and neuroanatomical substrates in the preweanling rat.
The first aim i s to describe in detail the locomotor behavior elicited by I-DOPA at different stages of ontogeny. L-DOPA-induced air-stepping has revealed largely unsuspected capacities for highly patterned locomotor movements in the neonatal rat. Air-stepping will be compared with treadmill walking and swimming to determine how biomechanical factors, reflexes, and sensory feedback interact with central nervous system (CNS) maturation in the production of locomotor behavior at different stages of maturity. At present, there are no quantitative data bearing on these issues.
The second aim i s to identify the neuropharmacological substrate(s) critical for 1-DOPA-induced air-stepping. The effects of agonists for receptor subtypes of both dopamine and noradrenaline will be tested. Thus the role(s) of the catecholamines in locomotor development will be fully described for the first time.
The third aim i s to identify the subdivision of the central nervous system necessary for drug-induced air-stepping at each age studied during preweanling ontogeny. Midthoracic spinal transection and precollicular decerebration will be used to grossly localize locomotor mechanisms activated by catecholamine agonists. These experiments will enable us to estimate the contributions of different levels of the CNS to the maturation of locomotion. The long-term goal of this research program is to identify and quantify developmental changes in locomotor parameters, and to identify their anatomical and pharmacological substrates. Because the principles of locomotor development in rats and humans are remarkably similar, the results will be relevant to our understanding of human locomotor development.
| McEwen, M L; Van Hartesveldt, C; Stehouwer, D J (1999) The NMDA antagonist, MK-801, alters L-DOPA-induced air-stepping in neonatal rats. Brain Res Dev Brain Res 115:33-40 |
| McEwen, M L; Van Hartesveldt, C; Stehouwer, D J (1997) A kinematic comparison of L-DOPA-induced air-stepping and swimming in developing rats. Dev Psychobiol 30:313-27 |
| McEwen, M L; Van Hartesveldt, C; Stehouwer, D J (1997) L-DOPA and quipazine elicit air-stepping in neonatal rats with spinal cord transections. Behav Neurosci 111:825-33 |
| McCrea, A E; Stehouwer, D J; Van Hartesveldt, C (1997) Dopamine D1 and D2 antagonists block L-DOPA-induced air-stepping in decerebrate neonatal rats. Brain Res Dev Brain Res 100:130-2 |
| Arnaiz, C O; Taylor, L L; Stehouwer, D J et al. (1996) An aromatic L-amino acid decarboxylase inhibitor blocks L-dopa-induced air-stepping in neonatal rats. Brain Res Dev Brain Res 94:234-7 |
| Taylor, L L; Sickles, A E; Stehouwer, D J et al. (1994) Noradrenergic alpha-1 and alpha-2 antagonists block L-dopa-induced air-stepping in neonatal rats. Brain Res Dev Brain Res 79:242-8 |
| Stehouwer, D J; McCrea, A E; Van Hartesveldt, C (1994) L-dopa-induced air-stepping in preweanling rats. II. Kinematic analyses. Brain Res Dev Brain Res 82:143-51 |
| McCrea, A E; Stehouwer, D J; Van Hartesveldt, C (1994) L-dopa-induced air-stepping in preweanling rats. I. Effects of dose and age. Brain Res Dev Brain Res 82:136-42 |
| Sickles, A E; Stehouwer, D J; Van Hartesveldt, C (1992) Dopamine D1 and D2 antagonists block L-dopa-elicited air-stepping in neonatal rats. Brain Res Dev Brain Res 68:17-22 |
