Neurochemical and behavioral consequences of striatal injection of 5,7-dihydroxytryptamine.
It is known that central serotonin (5HT) is involved in anxiety, but the behavioral results of many studies have been inconsistent. A prevalent research approach is to destroy 5HT neurotoxically. Such lesions were mostly generated by injecting 5,7-dihydroxytryptamine into ventricles or raphé nuclei, leading to rather global losses of 5HT in the brain. However, there is evidence for differential effects of 5HT in different brain structures regarding anxiety. Therefore, we decided to study the effects of injecting 5,7-dihydroxytryptamine into the forebrain. We chose the ventral striatum as the site of injection, since there is evidence that 5HT may be involved in anxiety there. We administered the neurotoxin bilaterally in adult rats, and analyzed neurochemical and behavioral consequences in three experiments. The first one showed that the toxin dose-dependently (10-50 microg) depleted 5HT in the ventral striatum, neostriatum, frontal cortex, and amygdala. Besides 5HT, dopamine was also partly depleted there. This dopaminergic lesion was prevented in a second experiment, where rats were pre-treated systemically with the dopamine reuptake inhibitor nomifensine. In the final experiment, the functional consequences of such 5HT lesions were tested, which yielded moderate anxiogenic effects in the elevated plus maze and in the open field. Also, there were lesion effects on aversively motivated ultrasonic vocalization during an active avoidance test. In contrast, active avoidance performance itself and general activity in the open field were not affected. Lesion effects became discernible there when challenging rats with MDMA. The psycho-stimulatory effectiveness of this drug, which acts largely via the availability of 5HT in the brain, was reduced to degrees that depended on the size of 5HT lesion. These results are discussed with respect to factors such as severity of lesion, anatomical specificity, and the role of 5HT in anxiety.
Ludwig
Verena
V
Experimental and Physiological Psychology, Philipps-University of Marburg, Gutenbergstrasse 18, 35037 Marburg, Germany. ludwigv@staff.uni-marburg.de
Schwarting
Rainer K W
RK
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000494:pharmacology; D004867:Equipment Design; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D006897:Hydroxyindoleacetic Acid / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology
D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine