Differential effect of NMDA on extracellular serotonin in rat midbrain raphe and forebrain sites.
ABSTRACT The contribution of NMDA receptors to regulation of serotonin (5-HT) release was assessed by in vivo microdialysis in freely behaving rats. During infusion of NMDA (30, 100, and 300 microM) into the dorsal raphe nucleus (DRN), 5-HT was increased by approximately 25, 100, and 280%, respectively. Competitive and noncompetitive NMDA-receptor antagonists blocked this effect on DRN 5-HT. Infusion of NMDA (300 microM) into the DRN also produced an 80% increase in extracellular 5-HT in the nucleus accumbens. During infusion of NMDA (100 and 300 microM) into the median raphe nucleus (MRN), 5-HT was increased by approximately 15 and 80%, respectively. NMDA-receptor antagonists blocked this effect on MRN 5-HT. Infusion of NMDA into the MRN also produced a significant increase in hippocampal 5-HT. In contrast, infusion of NMDA into the nucleus accumbens, frontal cortex, or hippocampus produced small decreases in 5-HT in these forebrain sites. Taken together, these results suggest that NMDA receptors in the midbrain raphe, but not the forebrain, can have an excitatory influence on 5-HT neurons and, thus, produce increased 5-HT release in the forebrain. Furthermore, in comparison with the MRN, DRN 5-HT neurons were more sensitive to the excitatory effect of NMDA.
Article: Functional interrelations between nucleus raphé dorsalis and nucleus raphé medianus: a dual probe microdialysis study of glutamate-stimulated serotonin release.[show abstract] [hide abstract]
ABSTRACT: Dual-probe in vivo microdialysis was used to explore the relationships between the two midbrain raphé nuclei, raphé dorsalis (DRN) and raphé medianus (MRN). Infusion of the excitatory neurotransmitter glutamate (10 mM) into the dorsal raphé nucleus produced a large increase in the extracellular 5-HT (5-HT(ext)) in the dorsal raphé (1400% of control values) that was limited to the time of infusion. This was followed by a significant decrease in extracellular 5-HT below baseline levels that continued for the duration of the experiment (3 h). Extracellular 5-HT (5-HT(ext)) was also increased to 500% of control values in the median raphé nucleus following infusion of 10 mM glutamate (GLU) into the dorsal raphé nucleus. Infusion of the competitive NMDA receptor antagonist AP5 prior to and during infusion of GLU into the DRN resulted in a decrease in the response to GLU in the DRN and an antagonism of the increase of 5-HT(ext) in the MRN. Infusion of 10mM GLU into the lateral midbrain tegmentum, an area of the brain just lateral to the DRN, also increased 5-HT(ext) in the probe in the lateral midbrain tegmentum (900% of control) but did not alter 5-HT(ext) in the MRN. When glutamate was infused into the MRN, 5-HT(ext) was also increased to 1400% of control in a time course similar to that seen with infusion of GLU into the DRN. Infusion of glutamate into the MRN, however, did not alter the 5-HT(ext) in the DRN. These data suggest a serotonergic innervation of the median raphé nucleus by the dorsal raphé nucleus. A reciprocal innervation from the median raphé to the dorsal raphé is not mediated by glutamate, does not appear to be serotonergic, and does not regulate extracellular serotonin in the dorsal raphé.Brain research bulletin 11/2008; 78(4-5):132-8. · 2.18 Impact Factor
Article: Neural Circuit in the Dorsal Raphe Nucleus Responsible for Cannabinoid-Mediated Increases in 5-HT Efflux in the Nucleus Accumbens of the Rat Brain.[show abstract] [hide abstract]
ABSTRACT: In vivo microdialysis was used in this study to reveal the role of cannabinoids in regulating serotonin (5-HT) efflux in the nucleus accumbens (NAcc) and dorsal raphe nucleus (DRN). The cannabinoid CB1 receptor agonists WIN55212-2 and CP55940 systematically administered to rats caused significant increases in 5-HT efflux in the NAcc but failed to have an effect in the DRN. To reveal mechanisms underlying regionally selective responses, we tested the hypothesis that cannabinoids have both direct and indirect effects on 5-HT efflux, depending on the location of CB1 receptors in the neural circuit between DRN and NAcc. We showed that the direct effect of cannabinoids caused a reduction in 5-HT efflux whereas the indirect effect resulted in an increase. Furthermore, the indirect effect was blocked by the GABA(A) receptor antagonist bicuculline in the DRN, suggesting that the action is likely due to a presynaptic inhibition on GABAergic activity that exerts a tonic influence on neuronal circuits regulating 5-HT efflux. Involvement of GABAergic neurons was confirmed by measuring changes in GABA efflux. Taken together, our study suggests that cannabinoids may have direct and indirect effects on the 5-HT regulatory circuits, resulting in regionally selective changes of 5-HT efflux in the brain.ISRN pharmacology. 01/2012; 2012:276902.
Article: The consequences of uncontrollable stress are sensitive to duration of prior wheel running.[show abstract] [hide abstract]
ABSTRACT: The behavioral consequences of uncontrollable stress, or learned helplessness (LH) behaviors, are thought to involve hyperactivity of serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). Other brain regions implicated in LH and capable of affecting 5-HT systems, such as the bed nucleus of the stria terminalis (BNST), amygdala, and habenula, could contribute to DRN 5-HT hyperactivity during uncontrollable stress. Six weeks of wheel running prevents LH and attenuates uncontrollable stress-induced c-Fos expression in DRN 5-HT neurons, although the duration of wheel running necessary for these effects is unknown. In the current study, 6 but not 3, weeks of wheel running blocked the shuttle box escape deficit and exaggerated fear produced by uncontrollable tail shock in sedentary rats. Corresponding to the duration-dependent effects of wheel running on LH behaviors, 6 weeks of wheel running was required to attenuate uncontrollable stress-induced 5-HT neural activity, indexed by c-Fos protein expression, in the DRN and c-Fos expression in the lateral ventral region of the BNST. Wheel running, regardless of duration, did not affect c-Fos expression anywhere in the amygdala or habenula. These data indicate that the behavioral effects of uncontrollable stress are sensitive to the duration of prior physical activity and are consistent with the hypothesis that attenuation of DRN 5-HT activity contributes to the prevention of LH by wheel running. The potential role of the BNST in the prevention of LH by wheel running is discussed.Brain Research 03/2005; 1033(2):164-78. · 2.73 Impact Factor