Behavioral and neurochemical consequences of repeated nicotine treatment in the serotonin-depleted rat.
BACKGROUND
Repeated exposure to addictive drugs causes neuroadaptive alterations that are proposed to increase the incentive motivation to consume drugs and to decrease the ability to inhibit such inappropriate motivational impulses and responses. Together, these behavioral consequences of drug intake may underlie the compulsive drug-seeking and -taking behaviors observed in drug abuse.


OBJECTIVE
Brain serotonin (5-HT) has been implicated in these mechanisms and this study therefore investigated the consequences of brain 5-HT depletion on the behavioral and neurochemical effects induced by repeated daily nicotine treatment (15 days) in male rats.


METHODS
The effects of the present pharmacological manipulations were evaluated behaviorally (locomotor activity, the elevated plus-maze) and neurochemically (microdialysis, brain biochemistry).


RESULTS
Depletion of brain 5-HT produced behavioral disinhibition in the elevated plus-maze. In 5-HT-depleted animals, nicotine-induced locomotor sensitization was observed on treatment days 5, 10, and 15, but only on day 15 in the sham-operated rats. Postsensitization, the locomotor stimulatory effects of amphetamine and the dopamine receptor agonists SKF 38,393, apomorphine, and quinpirole were decreased in 5-HT-depleted animals, an effect that appeared to be more pronounced in nicotine-treated rats. Repeated nicotine treatment sensitized the nicotine-induced elevation of the extracellular accumbal dopamine levels in sham-operated, but not in 5-HT-depleted rats, and was also associated with decreased D2 autoreceptor function in both nicotine-treated experimental groups.


CONCLUSIONS
Depletion of brain 5-HT, which produces behavioral disinhibition, may slightly facilitate the overall expression of locomotor sensitization to nicotine and differentially affect the pre- and postsynaptic neuroadaptive events involved in the expression of these phenomena.
Olausson
P
P
Department of Pharmacology, Göteborg University, Box 431, 405 30 Göteborg, Sweden. peter.olausson@yale.edu
Akesson
P
P
Petersson
A
A
Engel
J A
JA
Söderpalm
B
B
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology
D018491:Dopamine Agonists; D018722:Nicotinic Agonists; D018490:Serotonin Agents; D019257:Quinpirole; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009538:Nicotine; D004298:Dopamine