title: High and low responders to novelty: effects of a catecholamine synthesis inhibitor on novelty-induced changes in behaviour and release of accumbal dopamine.
abstract: The purpose of the present study was two-fold: (i) to investigate to what extent novelty, i.e. a novel cage with slightly larger dimensions than the home cage and lacking the floor covering that was originally present, produced behavioural effects in high responders to novelty and low responders to novelty that could be correlated with the extracellular amount of accumbal dopamine, using the microdialysis technique, and (ii) to establish the ability of the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine to inhibit the novelty-induced responses in high and low responders. The difference in the behavioural response to novelty between the high and low responders was limited to walking, which lasted significantly longer in high responders than in low responders. The novelty-induced increase in extracellular concentration of accumbal dopamine was significantly greater in high responders than in low responders; moreover, the shape of the growth curves differed between high and low responders. The behavioural changes did not correlate with the neurochemical effects, which outlasted the duration of the novelty-induced behavioural arousal. It is hypothesized that this long-lasting increase in accumbal dopamine produces "adaptive changes" that help and/or allow the animal to incorporate knowledge about the condition that it experienced. When the nucleus accumbens was perfused with alpha-methyl-p-tyrosine for a period of 40 min, given at the same time as the transfer of the rat to the novel cage, it reduced the novelty-induced increase in walking in the high responders, but did not alter the novelty-induced behaviour of low responders. Finally, alpha-methyl-p-tyrosine reduced the novelty-induced increase in the release of accumbal dopamine in high responders, but enhanced it in low responders. The present neurochemical data are discussed in view of the outcome of earlier reported pharmacobehavioural studies on the neurochemical state of the nucleus accumbens of non-challenged versus challenged high and low responders. It is hypothesized that, in the high responder, exposure to novelty enhances the release of accumbal dopamine from reserpine-resistant, alpha-methyl-p-tyrosine-sensitive pools that are under the stimulatory control of beta-adrenergic receptors in the nucleus accumbens, and that, in the low responder, exposure to novelty enhances the release of accumbal dopamine from reserpine-sensitive, alpha-methyl-p-tyrosine-resistant pools that are under the inhibitory control of alpha-adrenergic receptors in the nucleus accumbens.
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Saigusa
authors.forename: T
authors.initials: T
authors.lastname: Tuinstra
authors.forename: N
authors.initials: N
authors.lastname: Koshikawa
authors.forename: A R
authors.initials: AR
authors.lastname: Cools
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002395:Catecholamines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D019805:alpha-Methyltyrosine / Q000494:pharmacology*
chemical_list: D002395:Catecholamines; D004791:Enzyme Inhibitors; D019805:alpha-Methyltyrosine; D004298:Dopamine