Lesioning of locus coeruleus projections by DSP-4 neurotoxin treatment: effect on amphetamine-induced hyperlocomotion and dopamine D2 receptor binding in rats.
DSP-4 is a neurotoxin highly selective for the noradrenergic nerve terminals of the locus coeruleus projections. Data on the effect of DSP-4 treatment on amphetamine-induced hyperlocomotion are contradictory. In this study, DSP-4 (50 mg/kg) caused reduction of noradrenaline levels by 70% in the cerebral cortex and by 79% in the cerebellum. This treatment resulted in upregulation of dopamine D2 receptors in the striatum as evidenced by [3H]-raclopride binding. In an open field test, DSP-4 reduced locomotor activity. D-Amphetamine (1.5 mg/kg) caused a similar increase in locomotor activity in control and DSP-4-pretreated animals not familiar to the apparatus. However, when the rats were habituated to the test apparatus, the effect of amphetamine on horizontal activity was significantly larger in the DSP-4-pretreated animals. These data suggest that supersensitivity of D2 receptors develops after locus coeruleus denervation, but that the enhanced efficacy of amphetamine in DSP-4-treated rats is masked by neophobia.
Harro
J
J
Department of Psychology, University of Tartu, Estonia. jharro@ut.ee
Meriküla
A
A
Lepiku
M
M
Modiri
A R
AR
Rinken
A
A
Oreland
L
L
D000818:Animals; D001596:Benzylamines / Q000633:toxicity*; D003913:Dextroamphetamine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D020891:Raclopride / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015854:Up-Regulation
D001596:Benzylamines; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D020891:Raclopride; C012102:DSP 4; D003913:Dextroamphetamine; D009638:Norepinephrine