SEROTONERGIC LESIONS ALTER COCAINE-INDUCED LOCOMOTOR BEHAVIOR AND STRESS-ACTIVATION OF THE MESOCORTICOLIMBIC DOPAMINE SYSTEM

The aim of this study was to examine the effects of serotonergic lesio ns to the dorsal raphe on midbrain dopaminergic systems. 5,7-Dihydroxy tryptamine lesions of the dorsal raphe resulted in a substantial loss of serotonin in the medial prefrontal cortex (about 75%) and the nucle us accumbens (about 50%), while no change in DA levels or DA metabolis m were noted in either region at 12 days postlesion. A transient basal locomotor activation was noted in the lesioned animals compared to th e sham controls 7 to 12 days after the lesions. The locomotor response to an acute dose of cocaine was also enhanced in 5,7-dihydroxytryptam ine lesioned rats, however, no change in the time course or magnitude of the behavioral locomotor response to repeated cocaine administratio n was observed. Restraint for 30 min increased DA metabolism in both t he NAS and mPFC of sham rats, as expected. However, in 5,7-dihydroxytr yptamine lesioned rats, restraint stress enhanced the usual stress-ind uced increase in DA metabolism by about 50 and 150% in the medial pref rontal cortex and nucleus accumbens, respectively. Our results indicat e the 5,7-dihydroxytryptamine lesions of the dorsal raphe lower seroto nin in both the mPFC and NAS leading to an enhanced responsiveness of the DA projections in both regions. This effect may be explained by a loss of sensitivity of DA receptors in 5,7-dihydroxytryptamine denerva ted rats. This interpretation implies that the stimulated, but not bas al, release of DA in the mPFC and NAS is dependent on serotonin tone. (C) 1996 Wiley-Liss, Inc.