5‐HT1A receptor‐mediated inhibition and 5‐HT2 as well as 5‐HT3 receptor‐mediated excitation in different subdivisions of the rat amygdala

Abstract

The techniques of extracellular single cell recording and microiontophoresis were used to study the effects of serotonin (5-HT) and of 5-HT(1A), 5-HT(2A/2C) and 5-HT(3) receptor agonists on the spontaneous activity of amygdaloid neurons in rats anesthetized with urethane. The background discharge rate was modified by 5-HT as well as by 5-HT agonists in about two-thirds of neurons tested in different nuclei of the amygdaloid complex. Whereas the 5-HT(2) and 5-HT(3) agonists significantly increased the neuronal discharge rate in nearly all subdivisions of the amygdala, the 5-HT(1A) agonist significantly inhibited the firing rate. Co-administration of bicuculline and 5-HT receptor agonists prevented the 8-OH-DPAT-induced increases in the firing rate in most cases tested, as well as the inhibitory effects of DOI or 2-methyl-5HT. Therefore, GABAergic interneurons seem to be involved in the mediation of serotonergic effects. The action of 5-HT agonists on the neuronal discharge rate was blocked by different receptor-specific antagonists. The results support the hypothesis that 5-HT exerts control throughout the amygdala by acting at least on 5-HT(1A), 5-HT(2A/2C) and 5-HT(3) receptors seemingly located both on projection and interneurons.

Distribution of 5-HT2A receptor immunoreactivity in the rat amygdaloid complex and colocalization with γ-aminobutyric acid

“…The expression of the 5-HT2Ar in many pyramidal neuronal dendrites is consistent with a recent ultrastructural study demonstrating that the serotonin terminals in the anterior subdivision of the basal nucleus (called magnocellular and intermediate subdivisions of the basal nucleus in this paper) form both synaptic and appositional contacts with the distal dendrites of the pyramidal cells (Muller et al, 2007). The finding that the 5-HT2Ar is expressed by pyramidal neurons also correlates with electrophysiological studies demonstrating that the injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A/5-HT2C agonist, increased the discharge rate (Stein et al, 2000) and facilitated synaptic plasticity via an NMDA-mediated mechanism (Chen et al, 2003) in the presumptive pyramidal neurons of the basolateral amygdala. Interestingly, in the dendrites of the cortical pyramidal cells, the 5-HT2Ar is colocalized with MAP1A (Cornea-Hébert et al, 2002).…”

Distribution of 5-HT2A receptor immunoreactivity in the rat amygdaloid complex and colocalization with γ-aminobutyric acid

“…The expression of the 5-HT2Ar in many pyramidal neuronal dendrites is consistent with a recent ultrastructural study demonstrating that the serotonin terminals in the anterior subdivision of the basal nucleus (called magnocellular and intermediate subdivisions of the basal nucleus in this paper) form both synaptic and appositional contacts with the distal dendrites of the pyramidal cells (Muller et al, 2007). The finding that the 5-HT2Ar is expressed by pyramidal neurons also correlates with electrophysiological studies demonstrating that the injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A/5-HT2C agonist, increased the discharge rate (Stein et al, 2000) and facilitated synaptic plasticity via an NMDA-mediated mechanism (Chen et al, 2003) in the presumptive pyramidal neurons of the basolateral amygdala. Interestingly, in the dendrites of the cortical pyramidal cells, the 5-HT2Ar is colocalized with MAP1A (Cornea-Hébert et al, 2002).…”

Pattern of distribution of serotonergic fibers to the amygdala and extended amygdala in the rat

“…Although this finding appears inconsistent with a proposed role for 5‐HT 2C receptors in anxiogenesis (i.e., the activation, not the suppression, of principal BLA activity is thought to be anxiogenic), it should be noted that 1) a nonspecific 5‐HT 2 agonist was used (α‐methyl‐5‐HT); results may differ with a more specific 5‐HT 2c agonist; and 2) high concentrations or the prolonged application of 5‐HT suppressed the excitatory action of 5‐HT on BLA interneurons, and hence their inhibitory effect on PCs. Furthermore, in contrast to these results, Stein et al, () showed, in intact rats, that the 5‐HT 2C agonist DOI increased the activity of virtually all principal BLA neurons, whereas Reznikov et al () reported that restraint stress produced elevated levels of c‐fos expression in the vast majority of PCs of BLA. Taken together, these findings would indicate that 5‐HT 2/2C receptor cell activation excites both interneurons and principal cells of BLA, but, as noted by Campbell and Merchant (), the likely net effect would be an “augmentation of BLA output, which could underlie the anxiogenic responses of 5‐HT 2C agonists at behaviorally relevant doses.”…”

“…With some exceptions (see below) increases in BLA pyramidal cell activity appear to be anxiogenic, decreases anxiolytic. With respect to 5‐HT 1A receptors, an early report in anesthetized rats (Stein et al, ) showed that the 5‐HT 1A agonist 8‐OH‐DPAT suppressed the activity of most pyramidal cells (PCs) of BLA. In accordance with this, Cheng et al () showed that serotonin, acting via 5‐HT 1A receptors, suppressed the activity of principal BLA cells and reduced a depolarization‐evoked influx of calcium into these cells.…”

Neuronal localization of 5-HT2A receptor immunoreactivity in the rat hippocampal region

“…Fewer, but still a significant percentage of GABAergic double-labeled cells were also present in layers I and II. Consequently, as observed in the cortex [72,84,103] and amygdala [38,74,[81][82][83], in the parahippocampal region, the serotonin could also activate the 5-HT2Ar in GABAergic neurons to increase synaptic GABA input on the pyramidal cells. The entorhinal cortex shows a modular organization comparable to the columnar organization of the neocortex [97].…”

Distribution of 5-HT2A receptor immunoreactivity in the rat amygdaloid complex and colocalization with γ-aminobutyric acid

“…The expression of the 5-HT2Ar in many pyramidal neuronal dendrites is consistent with a recent ultrastructural study demonstrating that the serotonin terminals in the anterior subdivision of the basal nucleus (called magnocellular and intermediate subdivisions of the basal nucleus in this paper) form both synaptic and appositional contacts with the distal dendrites of the pyramidal cells (Muller et al, 2007). The finding that the 5-HT2Ar is expressed by pyramidal neurons also correlates with electrophysiological studies demonstrating that the injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A/5-HT2C agonist, increased the discharge rate (Stein et al, 2000) and facilitated synaptic plasticity via an NMDA-mediated mechanism (Chen et al, 2003) in the presumptive pyramidal neurons of the basolateral amygdala. Interestingly, in the dendrites of the cortical pyramidal cells, the 5-HT2Ar is colocalized with MAP1A (Cornea-Hébert et al, 2002).…”

Pattern of distribution of serotonergic fibers to the amygdala and extended amygdala in the rat

“…Although this finding appears inconsistent with a proposed role for 5‐HT 2C receptors in anxiogenesis (i.e., the activation, not the suppression, of principal BLA activity is thought to be anxiogenic), it should be noted that 1) a nonspecific 5‐HT 2 agonist was used (α‐methyl‐5‐HT); results may differ with a more specific 5‐HT 2c agonist; and 2) high concentrations or the prolonged application of 5‐HT suppressed the excitatory action of 5‐HT on BLA interneurons, and hence their inhibitory effect on PCs. Furthermore, in contrast to these results, Stein et al, () showed, in intact rats, that the 5‐HT 2C agonist DOI increased the activity of virtually all principal BLA neurons, whereas Reznikov et al () reported that restraint stress produced elevated levels of c‐fos expression in the vast majority of PCs of BLA. Taken together, these findings would indicate that 5‐HT 2/2C receptor cell activation excites both interneurons and principal cells of BLA, but, as noted by Campbell and Merchant (), the likely net effect would be an “augmentation of BLA output, which could underlie the anxiogenic responses of 5‐HT 2C agonists at behaviorally relevant doses.”…”

“…With some exceptions (see below) increases in BLA pyramidal cell activity appear to be anxiogenic, decreases anxiolytic. With respect to 5‐HT 1A receptors, an early report in anesthetized rats (Stein et al, ) showed that the 5‐HT 1A agonist 8‐OH‐DPAT suppressed the activity of most pyramidal cells (PCs) of BLA. In accordance with this, Cheng et al () showed that serotonin, acting via 5‐HT 1A receptors, suppressed the activity of principal BLA cells and reduced a depolarization‐evoked influx of calcium into these cells.…”

Neuronal localization of 5-HT2A receptor immunoreactivity in the rat hippocampal region

“…Fewer, but still a significant percentage of GABAergic double-labeled cells were also present in layers I and II. Consequently, as observed in the cortex [72,84,103] and amygdala [38,74,[81][82][83], in the parahippocampal region, the serotonin could also activate the 5-HT2Ar in GABAergic neurons to increase synaptic GABA input on the pyramidal cells. The entorhinal cortex shows a modular organization comparable to the columnar organization of the neocortex [97].…”

Distribution of 5-HT2A receptor immunoreactivity in the rat amygdaloid complex and colocalization with γ-aminobutyric acid

“…The expression of the 5-HT2Ar in many pyramidal neuronal dendrites is consistent with a recent ultrastructural study demonstrating that the serotonin terminals in the anterior subdivision of the basal nucleus (called magnocellular and intermediate subdivisions of the basal nucleus in this paper) form both synaptic and appositional contacts with the distal dendrites of the pyramidal cells (Muller et al, 2007). The finding that the 5-HT2Ar is expressed by pyramidal neurons also correlates with electrophysiological studies demonstrating that the injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A/5-HT2C agonist, increased the discharge rate (Stein et al, 2000) and facilitated synaptic plasticity via an NMDA-mediated mechanism (Chen et al, 2003) in the presumptive pyramidal neurons of the basolateral amygdala. Interestingly, in the dendrites of the cortical pyramidal cells, the 5-HT2Ar is colocalized with MAP1A (Cornea-Hébert et al, 2002).…”

Pattern of distribution of serotonergic fibers to the amygdala and extended amygdala in the rat

“…Although this finding appears inconsistent with a proposed role for 5‐HT 2C receptors in anxiogenesis (i.e., the activation, not the suppression, of principal BLA activity is thought to be anxiogenic), it should be noted that 1) a nonspecific 5‐HT 2 agonist was used (α‐methyl‐5‐HT); results may differ with a more specific 5‐HT 2c agonist; and 2) high concentrations or the prolonged application of 5‐HT suppressed the excitatory action of 5‐HT on BLA interneurons, and hence their inhibitory effect on PCs. Furthermore, in contrast to these results, Stein et al, () showed, in intact rats, that the 5‐HT 2C agonist DOI increased the activity of virtually all principal BLA neurons, whereas Reznikov et al () reported that restraint stress produced elevated levels of c‐fos expression in the vast majority of PCs of BLA. Taken together, these findings would indicate that 5‐HT 2/2C receptor cell activation excites both interneurons and principal cells of BLA, but, as noted by Campbell and Merchant (), the likely net effect would be an “augmentation of BLA output, which could underlie the anxiogenic responses of 5‐HT 2C agonists at behaviorally relevant doses.”…”

“…With some exceptions (see below) increases in BLA pyramidal cell activity appear to be anxiogenic, decreases anxiolytic. With respect to 5‐HT 1A receptors, an early report in anesthetized rats (Stein et al, ) showed that the 5‐HT 1A agonist 8‐OH‐DPAT suppressed the activity of most pyramidal cells (PCs) of BLA. In accordance with this, Cheng et al () showed that serotonin, acting via 5‐HT 1A receptors, suppressed the activity of principal BLA cells and reduced a depolarization‐evoked influx of calcium into these cells.…”

Neuronal localization of 5-HT2A receptor immunoreactivity in the rat hippocampal region

“…Fewer, but still a significant percentage of GABAergic double-labeled cells were also present in layers I and II. Consequently, as observed in the cortex [72,84,103] and amygdala [38,74,[81][82][83], in the parahippocampal region, the serotonin could also activate the 5-HT2Ar in GABAergic neurons to increase synaptic GABA input on the pyramidal cells. The entorhinal cortex shows a modular organization comparable to the columnar organization of the neocortex [97].…”