Potentiation of the effects of reward-related stimuli by dopaminergic-dependent mechanisms in the nucleus accumbens.
Three experiments examined the behavioural, pharmacological and neural specificity of the previously reported potentiation of responding with conditioned reinforcement following intra-accumbens d-amphetamine, by studying the effects of intra-accumbens dopamine (DA) and noradrenaline, using an acquisition of a new response procedure. In experiment 1, the effects of intra-cerebral DA infusions (5, 20, 50 micrograms/2 microliters) were compared in four conditions: (i) intra-accumbens DA following positive pairing of the conditioned stimulus (CS) and water during training; (ii) as (i) but also following a systemic dose of the DA receptor antagonist alpha-flupenthixol; (iii) intra-accumbens DA following random pairing of the CS and water during training; and (iv) as (i) but with intra-caudate rather than intra-accumbens DA. The results showed that only with intra-accumbens DA in the positive pairing condition was there a significant dose-dependent increase in responding. In experiment 2, the effects of a higher range of doses (20, 100, 200 micrograms) and smaller infusion volume (5, 25, 50 micrograms/l microliters) of intra-accumbens DA were studied, in comparison with a similar range of doses (5, 25, 50 micrograms/l microliters) of intra-accumbens noradrenaline (NA). Only DA produced a selective, dose-dependent increase in responding with conditioned reinforcement. In experiment 3 neurotoxic lesions of the dorsal noradrenergic bundle (DNAB) using 6-hydroxydopamine producing profound (about 90%) depletion of cortical and nucleus accumbens NA levels had no effect on the increased responding with conditioned reinforcement produced by intra-accumbens d-amphetamine (3, 10, 30 micrograms/l microliters).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Experimental Psychology, University of Cambridge, UK.
M
M
Cador
J R
JR
Taylor
T W
TW
Robbins
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012201:Reward
D016627:Oxidopamine; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine