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Cocaine increases serotonergic activity in the hippocampus and nucleus accumbens in vivo: 5-HT1a-receptor antagonism blocks behavioral but potentiates serotonergic activation.

Abstract:
The hippocampus is an important mediator of learning and reinforcement, but its role in cocaine effects has received little attention. Neuronal activity in the hippocampus and the nucleus accumbens (Nac) depend on serotonergic (5-HT) transmission. Here we describe for the first time a cocaine-induced increase in 5-HT concentration in the hippocampus and the Nac parallel to behavioral activation. In addition, pretreatment with the 5-HT(1A)-receptor antagonist WAY 100635 blocked the behavioral activation after cocaine while potentiating the 5-HT increase in the hippocampus and the Nac. In vivo microdialysis was used in behaving rats to measure extracellular concentration of 5-HT in the hippocampus and the Nac. Four groups of animals received one of the following drug combinations: WAY 100635 (0.4 mg/kg) and cocaine (10 mg/kg), saline and cocaine (10 mg/kg), WAY 100635 (0.4 mg/kg) and saline, or saline and saline. The injections were administered i.p. and spaced 30 min apart. It was found that 1.) cocaine, at a dose that activates behavior, increases 5-HT levels in the hippocampus and in the Nac, and 2.) 5-HT(1A)-receptor antagonism can cause a dissociation of the hippocampal and Nac 5-HT activity from behavioral activation after cocaine. These results are discussed within the framework of the hippocampal-accumbens projection and its contribution to behavioral activity. They suggest that the hippocampus may have a role in mediating the behavioral and neurochemical effects of cocaine.

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Publisher copy:
10.1002/syn.10083

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author


Journal:
Synapse (New York, N.Y.) More from this journal
Volume:
45
Issue:
2
Pages:
67-77
Publication date:
2002-08-01
DOI:
EISSN:
1098-2396
ISSN:
0887-4476


Language:
English
Keywords:
Pubs id:
pubs:241329
UUID:
uuid:ac55cb96-e656-40d5-9221-48f135df9317
Local pid:
pubs:241329
Source identifiers:
241329
Deposit date:
2013-11-16

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