When placed in a tank of water, aged rats (24 to 27 months old) showed marked impairments in swimming. Compared with young adult rats (3 to 4 months old), the older animals moved their limbs less vigorously and were less successful in keeping their heads above water. The young, but not old, rats maintained a position nearly horizontal to the water surface and planed across it. These movement dysfunctions of aged rats resemble those seen in young adult animals that have sustained injury to brain dopamine-containing neurons. The swimming impairments of the aged rats were reversed by the dopamine receptor stimulant apomorphine and by the biosynthetic precursor of dopamine, L-dopa. Thus, age-related alterations in brain dopaminergic systems may be responsible for some of the movement disturbances associated with senescence.

Damage to the mesotelencephalic dopamine-containing projection of rats results in a sensory inattention, characterized by impairments in orientation toward somatosensory, visual, and olfactory stimuli. The present experiments were performed to establish which branch of this dopaminergic system is responsible for these sensorimotor deficits. Two approaches were used. In the first, individual dopamine-innervated forebrain sites were damaged by localized 6-hydroxydopamine injection into, or by electrolytic lesions of, these regions. In the second, rats were given tegmental 6-hydroxydopamine injections that damaged the entire mesotelencephalic projection and subsequently received intracerebral injections of the dopamine agonist apomorphine into specific forebrain sites in an attempt to reinstate orientation. The results demonstrate that dopaminergic terminals in the neostriatum are critical for orientation. Unilateral neostriatal 6-hydroxydopamine injections or electrolytic lesions reduced orientation to contralateral touch, whereas similar damage to other dopamine-innervated forebrain structures did not. Further, the results suggest that dopaminergic terminals in the anterior neostriatum are especially important for orientation to touch of the rostral body surface while those in the posterior neostriatum are most critical for orientation to caudal touch. After damage to all branches of the mesotelencephalic dopaminergic system, orientation to touch was reinstated by injection of apomorphine into the neostriatum but not by injection into the other dopamine-innervated forebrain regions tested.The dopamine-containing cell bodies of to tactile, visual, and olfactory stimuli the ventral mesencephalon of rats give rise (Ljungberg & Ungerstedt, 1976; Marshall, to long axons that ascend through the me-Richardson, & Teitelbaum, 1974) and show dian forebrain bundle to innervate multiple abnormalities of posture and limb use forebrain sites, including neostriatum . The orientational (caudate-putamen), nucleus accumbens impairments represent disturbances of septi, olfactory tubercle, frontal cortex, and sensorimotor integration that appear similar lateral septal nucleus (Lindvall & Bjorklund, to syndromes of "neglect" or "inattention" 1974; Ungerstedt, 1971b). This projection, in humans and other primates (Dennytermed the mesotelencephalic dopaminergic Brown & Chambers, 1958; Heilman & Watsystem, is essential for normal movement son, 1976). After unilateral 6-hydroxydoand attentiveness to stimuli. When this pamine (6-OHDA) injections that damage projection is destroyed, animals fail to orient these neurons, many rats completely recover their ability to orient to touch of the contralateral body surface within 1 mo postop-

Summary:Purpose: Excitatory amino acid transporter (EAAT) activity prevents Glu from reaching toxic levels, but their contribution to epileptogenesis remains controversial. We examined how the convulsant veratridine causes inhibition of EAAT activity and how it differs from the effects of another convulsant, high (50 mM) K + , that also increases Na + conductance.Methods: Transverse rat hippocampal slices were incubated for 1 h with 100 M veratridine in oxygenated artificial cerebrospinal fluid (aCSF) with or without extracellular Ca 2+ . The medium was replaced by 50 M [ 3 H]glutamate in aCSF, and the slices incubated for 10 min at 37°C. The slices were washed 3 times with cold aCSF after removal of the extracellular medium, and the radioactivity was quantified after solubilization of the slices.Results: Veratridine caused a time-and dose-dependent decrease, whereas high K + had no effect on EAAT activity. The effects of veratridine on EAAT activity were not prevented by tetrodotoxin (TTX; 10 M). Coincubation of ouabain with veratridine resulted in further decreases of EAAT activity. Removal of extracellular Ca 2+ potentiated the inhibitory effects of veratridine (and other convulsants) on EAAT activity. Chelation of intracellular Ca 2+ with BAPTA also increased the inhibitory effects of veratridine on EAAT activity.Conclusions: Veratridine caused changes Ca 2+ dynamics that led to inhibition of EAAT activity. Such changes in EAAT activity can contribute to the sustained epileptiform activity caused by veratridine.

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