The interplay between brain 5-hydroxytryptamine levels and cocaine addiction.
Cocaine addiction is a major health problem that affects millions of people. Cocaine acts by inhibiting dopamine, noradrenaline and serotonin [5-hydroxytryptamine(5-HT)] reuptake. The dopaminergic system is generally assumed to be involved in the reinforcing aspects of the drug, but the role of 5-HT in the addictive potential of cocaine is unclear. In light of pharmacological manipulations and cocaine use-related disease states affecting brain 5-HT levels, we review studies on the effect of cocaine on central 5-HT function. In addition, the contribution of 5-HT to the rewarding, aversive, discriminative and subjective, as well as the motivational and reinforcing effects of cocaine is discussed. We specifically focus on net changes in the extracellular 5-HT levels that occur as a consequence of acute and chronic cocaine exposure and how these influence cocaine abuse-related behaviour. Overall, the data indicate that 5-HT plays a major role in the psychomotor stimulant, rewarding and discriminative stimulant effects of cocaine, but also affects the motivational and reinforcing effects of the drug. In addition, 5-HT mediates, to some extent, the aversive effects of cocaine. Difficulties with data interpretation are discussed.
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Lourens J P
LJ
Nonkes
Inge P G
IP
van Bussel
Michel M M
MM
Verheij
Judith R
JR
Homberg
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D006801:Humans; D012054:Reinforcement, Psychology; D012701:Serotonin / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D012701:Serotonin; D003042:Cocaine