title: Effects of low dose N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine administration on exploratory and amphetamine-induced behavior and dopamine D2 receptor function in rats with high or low exploratory activity.
abstract: Individual differences in behavioral traits are associated with sensitivity to various neurochemical and psychopharmacological manipulations. In this study exploratory and amphetamine-induced behavior in rats with persistently high or low exploratory activity (HE and LE, respectively) was examined before and after a partial denervation of the locus coeruleus (LC) projections with the selective neurotoxin DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 10 mg/kg). Partial LC denervation prevented the increase in exploratory activity over repeated test sessions in the LE animals, but had no effect in HE-rats. Amphetamine- (0.5 mg/kg) induced locomotor activity was attenuated by DSP-4 pretreatment only in HE-rats. These results suggest differential involvement of LC noradrenergic transmission in novelty- and amphetamine-induced behavior in animals with persistent differences in novelty-related behavior. In addition to partial noradrenaline depletion in the frontal cortex and hippocampus, which occurred in both HE- and LE-rats, DSP-4 treatment also decreased the content of dopamine and its metabolites in the nucleus accumbens, and the metabolite levels in striatum, but only in the LE-animals. 5-HIAA levels were also reduced in the nucleus accumbens and striatum in LE-rats by the neurotoxin. D(2) receptor function, as determined by dopamine-stimulated [(35)S]GTPgammaS binding, was increased by DSP-4 treatment in the striatum of LE-rats, but reduced in HE-rats. No effect of partial LC denervation was found on dopamine-stimulated [(35)S]GTPgammaS binding in the nucleus accumbens. Together these findings suggest that LC noradrenergic neurotransmission is differently involved in dopaminergic mechanisms which mediate novelty-related vs amphetamine-induced behavior.
authors.affiliation: Department of Psychology, Centre of Behavioural and Health Sciences, University of Tartu, Estonia.
authors.forename: A
authors.initials: A
authors.lastname: Alttoa
authors.forename: K
authors.initials: K
authors.lastname: Kõiv
authors.forename: M
authors.initials: M
authors.lastname: Eller
authors.forename: A
authors.initials: A
authors.lastname: Uustare
authors.forename: A
authors.initials: A
authors.lastname: Rinken
authors.forename: J
authors.initials: J
authors.lastname: Harro
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000662:Amphetamines; D001596:Benzylamines; D014179:Neurotransmitter Uptake Inhibitors; D017448:Receptors, Dopamine D2; D019204:GTP-Binding Proteins; C012102:DSP 4; D004298:Dopamine