In vivo electrochemical measurements and electrophysiological studies of rat striatum following neonatal 6-hydroxydopamine treatment.
The effects of neonatal treatment (one day after birth) with the neurotoxin, 6-hydroxydopamine (75 micrograms/10 microliters intracisternal), were studied in the striatum of normal adult and treated Sprague-Dawley rats. Measurements of monoamine levels in the dorsal striatum and nucleus accumbens, by high-performance liquid chromatography coupled with electrochemical detection, showed that neonatal 6-hydroxydopamine treatment produced a permanent and massive destruction of striatal dopamine. The effects were more pronounced in the dorsal striatum than in the nucleus accumbens. In addition, serotonin levels were elevated in the rat striatum as a consequence of the neonatal treatment. Rapid chronoamperometric recordings of K(+)-evoked monoamine overflow using Nafion-coated recording electrodes were investigated in both the dorsal and ventral striatum of control and neonatally lesioned rats. The potassium-evoked responses recorded from the dorsal striatum of the 6-hydroxydopamine-treated rats were significantly reduced in amplitude as compared to controls. In addition, the reduction/oxidation current ratios of the responses were more serotonin-like, in contrast to the dopamine-like current ratios measured in the striatum of untreated animals. In ventral striatum, the amplitudes of the K(+)-evoked responses were not significantly reduced versus control. However, the K(+)-evoked signals were more serotonin-like in their electrochemical characteristics as compared to controls. In addition to the release studies, extracellular single-unit electrophysiological recordings were performed in normal and neonatally 6-hydroxydopamine-treated rats. The spontaneous discharge rate of striatal neurons in the neonatally 6-hydroxydopamine-treated rats was similar to that of control rats. This is in contrast to dopamine lesions in adult animals, where a marked elevation of the discharge rate is observed. Local applications of dopamine and serotonin into the striatum of neonatally 6-hydroxydopamine-treated rats elicited excitations of striatal cells rather than the normal inhibitory effects seen in control animals. Taken together, these data suggest that loss of striatal dopamine terminals at birth leads to both pre- and postsynaptic alterations in monoamine pathways.
Luthman
J
J
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Friedemann
M
M
Bickford
P
P
Olson
L
L
Hoffer
B J
BJ
Gerhardt
G A
GA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001205:Ascorbic Acid / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D004563:Electrochemistry / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D007839:Functional Laterality; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D005971:Glutamates; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine; D001205:Ascorbic Acid; D004298:Dopamine; D006719:Homovanillic Acid