Neonatal 6-hydroxydopa, but not DSP-4, elevates brainstem monoamines and impairs inhibitory avoidance learning in developing rats.
The involvement of brain monoamines in learning and memory in developing rats was studied by comparing the effects of 3 different noradrenergic neurotoxin treatments. Two experimental groups of male Sprague-Dawley rat pups were injected systemically with 50 micrograms/g of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) either on the day of birth or on postnatal days 17-18. Rats in the third experimental group were injected systemically with 60 micrograms/g of 6-hydroxydopa (6-OHDOPA) on postnatal days 0 and 2. Control littermates received vehicle. The animals were trained on an inhibitory avoidance task on postnatal days 27-29 and tested for retention 24 h later. The drug treatments produced comparable depletion of norepinephrine in the hippocampus and frontal cortex. 6-OHDOPA, but neither DSP-4 treatment, significantly elevated brainstem concentrations of norepinephrine and serotonin. In addition, 6-OHDOPA, but not DSP-4, significantly impaired retention of the inhibitory avoidance task. The impairment did not reflect insensitivity to the footshock used in training: both neonatal drug treatments tended to lower, not raise, footshock thresholds, as measured by a flinch test. High affinity choline uptake was not affected by either neonatal drug treatment in any of the brain areas examined. Thus, the 6-OHDOPA-induced behavioral deficit did not involve altered acetylcholine function. The results implicate brainstem monoamines in the modulation of learning and memory during development.
Cornwell-Jones
C A
CA
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Decker
M W
MW
Chang
J W
JW
Cole
B
B
Goltz
K M
KM
Tran
T
T
McGaugh
J L
JL
D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D001596:Benzylamines / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism* / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012153:Retention, Psychology / Q000187:drug effects*
D001596:Benzylamines; D015306:Biogenic Monoamines; D009498:Neurotoxins; C001388:6-hydroxydopa; D004295:Dihydroxyphenylalanine; C012102:DSP 4