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1.
Midbrain somatodendritic 5-HT1A autoreceptors play a central inhibitory role in the regulation of serotonergic neurotransmission. Given that serotonergic neurotransmission appears to be altered in experimental cholestatic liver disease we examined alterations in midbrain 5-HT1A autoreceptor binding and physiological responses in rats with experimental cholestatic liver disease in comparison to non-cholestatic controls. Using a standard receptor binding assay cholestatic rats exhibited an increase in midbrain 5-HT1A receptor number but no change in receptor affinity compared to controls. Midbrain 5-HT1A receptor mRNA expression as determined by semiquantitative RT-PCR was similar in cholestatic and non-cholestatic animals. In addition, cholestatic rats exhibited enhanced 5-HT1A autoreceptor-mediated hypothermic and hyperphagic responses compared to non-cholestatic controls after the administration of the highly specific 5-HT1A receptor agonist LY293284. These findings indicate that experimental cholestatic liver injury is associated with enhanced 5-HT1A autoreceptor-mediated physiological responsiveness in the setting of increased midbrain 5-HT1A receptor number but not affinity. 相似文献
3.
Recent studies have proposed an interrelation between the brain-derived neurotrophic factor (BDNF) val66met polymorphism and the serotonin system. In this study, we investigated whether the BDNF val66met polymorphism or blood BDNF levels are associated with cerebral 5-hydroxytryptamine 2A (5-HT 2A) receptor or serotonin transporter (SERT) binding in healthy subjects. No statistically significant differences in 5-HT 2A receptor or SERT binding were found between the val/val and met carriers, nor were blood BDNF values associated with SERT binding or 5-HT 2A receptor binding. In conclusion, val66met BDNF polymorphism status is not associated with changes in the serotonergic system. Moreover, BDNF levels in blood do not correlate with either 5-HT 2A or SERT binding. 相似文献
4.
Among drugs that act on serotonergic neurotransmission, selective serotonin (5-HT) reuptake inhibitors (SSRIs) are now the gold standard for the treatment of anxiety disorders. The precise mechanisms of the anxiolytic actions of SSRIs are unclear. We reviewed the literature related to the effects of SSRIs and the neurochemical changes of 5-HT in conditioned fear. Acute SSRIs and 5-HT 1A receptor agonists reduced the acquisition and expression of contextual conditioned fear. Chronic SSRI administration enhanced anxiolytic-like effects. Microinjection studies revealed the amygdala as the target brain region of both classes of serotonergic drugs, and the hippocampus as the target of 5-HT 1A receptor agonists. These findings highlight the contribution of post-synaptic 5-HT receptors, especially 5-HT 1A receptors, to the anxiolytic-like effects of serotonergic drugs. These results support the new 5-HT hypothesis of fear/anxiety: the facilitation of 5-HT neurotransmission ameliorates fear/anxiety. Furthermore, these behavioral data provide a new explanation of neurochemical adaptations to contextual conditioned fear: increased 5-HT transmission seems to decrease, not increase, fear. 相似文献
5.
There is considerable evidence for an involvement of serotonergic mechanisms in the control of alcohol consumption. In the present study, an extensive 5-HT 2A receptor autoradiographic investigation was carried out in two genetically selected rat strains, P and AA alcohol-preferring rats, respectively, as well as in the corresponding NP and ANA alcohol-nonpreferring rats. The aim was to determine if there is any common pattern in 5-HT 2A binding site densities that may illuminate mechanisms of alcohol preference in these animals. For quantitating 5-HT 2A binding sites, [ 3H]ketanserin (2 nM) was used. Nonspecific binding was measured in the presence of methysergide 10 −6 M. Results demonstrated a lower level (from 50 to 70%) of 5-HT 2A binding sites in the layer IV of prefrontal cortex, frontal cortex, parietal cortex of P rats compared to NP controls. Similarly, in the claustrum, 5-HT 2A binding density of P rats was 50% lower than that of NP rats, although this failed to achieve statistical significance. No difference was detected in the other areas investigated, including the olfactory tubercles, nucleus accumbens, caudate putamen, pyriform cortex, ventral tegmental area, temporal cortex, and entorhinal cortex. In AA rats, [ 3H]ketanserin binding density measured in these brain areas was very similar to that observed in ANA nonpreferring controls, and statistical analysis did not reveal any significant difference between the two rat lines. The present study confirms previous reports demonstrating lower densities of 5-HT 2A binding sites in the P rats and provides the first autoradiographic evidence showing that such an alteration does not occur in AA rats. These findings suggest that the expression of high alcohol preference in genetically selected P and AA rats is not associated with a shared neurochemical alteration of the 5-HT 2A receptor system. 相似文献
6.
Summary The density of 5-HT 1A binding using 3H-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) as binding ligand, was studied in human frontal cortex of suicide victims and normal controls who died due to medical disease or accidentally. There was no difference in the maximum number of binding site (B max) or K d (an inverse measure of affinity) of 5-HT 1A receptor binding sites between normal controls and the entire group of suicide victims. However, nonviolent suicides had significantly higher B max (22—25%) compared to both controls and violent suicides. A negative correlation between age and B max of 5-HT 1A binding sites was found in male controls but not in female controls or suicide victims. This relationship was less apparent among the male controls over age 60. 相似文献
7.
The 5-HT 1A and 5-HT 1B receptor systems play central roles in the control of serotonergic neurotransmission and feature prominently in many behaviors and physiological functions. In addition, the regulation of these receptors and their effector mechanisms has been the focus of intense interest because of their potential importance in the therapeutic actions of anxiolytic and antidepressant drugs. Here we describe the regulation of 5-HT 1A and 5-HT 1B receptor-mediated inhibition of adenylyl cyclase activity by receptors which activate phospholipid signaling cascades. Although it might be expected that these two highly homologous Gi-coupled receptors would be regulated similarly by activation of phospholipase C (PLC) and phospholipase A 2 (PLA 2), we have found that the regulation differs markedly between these receptor systems. Further, our data suggest that the modulation of agonist efficacy at these receptor subtypes is dependent on the nature of receptor coupling to PLC and PLA 2 activation. Moreover, regulation at the level of the effector (e.g., adenylyl cyclase) appears to play a significant role in the regulation of both the 5-HT 1A and 5-HT 1B receptor systems by the PLA 2 signaling cascade. Such data illustrate multiple levels for control of biochemical signaling cascades within cells and demonstrate that although different receptors may couple to the same effector pathways, the ultimate cellular effects produced by these receptors may differ due to differential cross-talk regulation. 相似文献
8.
The serotonin 1A (5-hydroxytryptamine [5-HT] 1A) receptors are members of a superfamily of seven transmembrane domain receptors that couple to G-proteins. Serotonergic signalling has been shown to play an important role in alcohol intake, preference and dependence. G-protein coupling of the 5-HT 1A receptor serves as an important determinant for serotonergic signalling. We have studied the effect of alcohols on G-protein coupling of bovine hippocampal 5-HT 1A receptors in native membranes. This was done by monitoring the modulation of ligand (agonist and antagonist) binding in presence of alcohols by guanosine-5′- O-(3-thiotriphosphate) (GTP-γ-S), a non-hydrolyzable analogue of GTP. Our results show that alcohols inhibit the specific binding of the agonist 8-hydroxy-2-(di- N-propylamino)tetralin (except in case of ethanol) and the antagonist 4-(2′-methoxy)-phenyl-1-[2′-( N-2″-pyridinyl)- p-fluorobenzamido]ethyl-piperazine to 5-HT 1A receptors in a concentration-dependent manner. Further, we show here that the action of alcohols on the bovine hippocampal 5-HT 1A receptors could be modulated by guanine nucleotides and that the mode of action of ethanol on the 5-HT 1A receptor may be quite different than that of other alcohols. The effect of GTP-γ-S on the agonist and the antagonist binding is found to be markedly different. Our results could be significant in the overall context of the role of G-protein coupling in serotonergic neurotransmission and its role in alcohol tolerance and dependence. 相似文献
9.
Several lines of evidence support the involvement of serotonergic (5-HT) neurons of the median raphe nucleus (MRN) in anxiety-like behaviour. In this context, it is known that blockade of 5-HT 1A somatodendritic autoreceptors in the midbrain raphe nuclei increases the firing rate of these neurons, disinhibiting 5-HT release in postsynaptic target areas such as amygdala, hippocampus and periaqueductal grey matter (PAG). However, while activation of 5-HT 1A or 5-HT 2 receptors in forebrain targets such as the amygdala or hippocampus enhances anxiety-like behaviours in rodents, stimulation of both receptor subtypes in the midbrain PAG markedly reduces anxiety-like behaviour. In view of these findings, the present study investigated whether the anti-anxiety effects induced by pharmacological disinhibition of 5-HT neurons in the MRN are attenuated by the blockade of 5-HT 2 receptors within the PAG. Mice received combined intra-PAG injection with ketanserin (10 nmol/0.1 μl), a 5-HT 2 receptor antagonist, followed by intra-MRN injection of WAY-100635 (5.6 nmol/0.1 μl), a highly selective 5-HT 1A receptor antagonist. They were then individually exposed to the elevated plus-maze (EPM), with the videotaped behavioural sessions subsequently scored for both conventional and ethological measures. The results confirmed that intra-MRN infusion of WAY100635 reduces behavioural indices of anxiety without significantly altering general activity measures, and further showed that this effect was completely blocked by intra-PAG pretreatment with an intrinsically-inactive dose of ketanserin. Together, these results suggest that 5HT 2 receptor populations located within the midbrain PAG play a significant role in the reduction of anxiety observed following disinhibition of 5-HT neurons in the MRN. 相似文献
10.
Summary. Serotonergic systems were investigated in the frontal cortex of rats with thioacetamide (TAA)-induced acute hepatic encephalopathy
(HE). Extracellular basal levels of 5-HT showed no difference between control and HE animals, whereas the levels of 5-HIAA
were significantly increased in HE rats. Unlike basal levels, high K +-evoked 5-HT release was significantly higher in HE rats than controls. B max of (±)-1-(2,5-dimethoxy-4- [ 125I] iodophenyl)-2-aminopropane ([ 125I] DOI) binding, mainly labeling postsynaptic 5-HT 2A receptors, was significantly decreased without any change in K d in HE rats. These results suggest that there is no change in basal 5-HT release in the cortex of rats with TAA-induced HE
despite the increase in intraneuronal 5-HT metabolism and in the size of releasable 5-HT pool, and that serotonergic neurotransmission
via 5-HT 2A receptor is altered in the brain area of rats with HE.
Accepted October 21, 1997 / Received April 29, 1997 相似文献
11.
[ 11C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT 2A) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [ 11C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT 2A receptors with [ 11C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [ 11C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [ 11C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT 2A receptor antagonist ketanserin before a second PET scan significantly decreased [ 11C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [ 11C]Cimbi-36 binding is selective for 5-HT 2A receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT 2A receptors in the human brain. Thus, we here describe [ 11C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT 2A receptors in the human brain. 相似文献
12.
In this study, we compared the localization of central 5-HT 1 binding sites of rat and guinea pig. The 5-HT 1B sites were absent in the guinea pig brain. Good correlations were found between species in the regional distribution of 5-HT 1 sites labelled with [ 3H]5-HT( r = 0.73), 5-HT 1A sites labelled with [ 3H]8-OH-DPAT ( r = 0.87), and 5-HT 1B versus 5-HT 1D sites labelled with [ 3H]5-HT in the presence of ipsapirone and DOI ( r = 0.76). Despite the overall similarities, species differences were observed in many brain regions. The CA1/CA2 fields of the hippocampus and the dorsal subiculum displayed significantly more 5-HT 1A receptor binding in guinea pig than in rat. Conversely, the 5-HT 1A binding in dorsolateral septum, cingulate cortex and laminae IV-V of the neocortex, was more pronounced in rat. Areas almost exclusively containing 5-HT 1B or 5-HT 1D sites, such as the ventral pallidum, globus pallidus and substantia nigra, expressed markedly more [ 3H]5-HT binding in rat as compared to guinea pig, while the opposite occurred in claustrum, dorsal endopiriform nucleus, lateral geniculate nucleus, and superficial grey layer of the superior colliculus. The implications of the species differences are illustrated by the binding of [ 3H]eltoprazine. The distribution of [ 3H]eltoprazine binding sites showed a good correlation with that of the 5-HT 1B sites in rat ( r = 0.89), and with that of the 5-HT 1A sites in guinea pig ( r = 0.97). The data give rise to the possibility that differences in the presence and distribution of 5-HT 1 receptor sites are related to species differences in behavioral, neurochemical and physiological responses to drugs with 5-HT 1 receptor affinity. 相似文献
13.
An electrophysiological study was performed using chloral hydrate-anesthetized rats to determine whether tandospirone, a 5-HT 1A agonist, affects neuronal activities of the medial vestibular nucleus (MVN), since serotonergic innervation and 5-HT 1A receptors are present in this nucleus. Tandospirone applied microiontophoretically at a current of 20–60 nA caused an inhibition of tilt-induced firing of α-type neurons, which showed increased and decreased firing with lateral tilt ipsilateral and contralateral to the recording site, respectively, along with that of β-type neurons which exhibited the reverse responses to ipsilateral and contralateral tilt stimulation. The inhibition was antagonized during simultaneous, iontophoretic application of WAY-100635 (20–60 nA), a 5-HT 1A receptor antagonist, although WAY-100635 alone rarely affected spontaneous or tilt-induced firing in either type of neurons. These results suggest that tandospirone acts on a 5-HT 1A receptor to inhibit transmission of otolith information to α- and β-type MVN neurons. 相似文献
14.
Middle age is associated with changes in circadian rhythms (e.g., alterations in the timing of the circadian wheel running rhythm) which resemble changes induced by selective destruction of the serotonergic input to the suprachiasmatic nucleus (SCN), the principal mammalian circadian pacemaker. We hypothesized that serotonergic neurotransmission in the SCN is decreased in middle-aged hamsters, as compared to young adults. This hypothesis was tested indirectly by investigating the effect of aging on two markers of serotonin neurotransmission, 5-HT 1B receptors and serotonin reuptake sites, which are regulated by serotonin. Previous studies have shown that experimentally induced decreases in serotonergic neurotransmission increase 5-HT 1B receptors but decrease serotonin reuptake sites. Quantitative autoradiography was conducted using [ 125I]iodocyanopindolol ([ 125I]ICYP) and [ 3H]paroxetine, selective radioligands for the 5-HT 1B receptors and the serotonin reuptake sites, respectively. Consistent with the hypothesis, specific ([ 125I]ICYP binding was significantly elevated in the SCN of middle-aged hamsters, as compared to young hamsters. The results also showed that serotonin reuptake sites in the SCN were significantly increased in both middle-aged and old hamsters, as compared to young controls. This result could not have been caused by decreased serotonin release. Alternatively, increased serotonin reuptake, which would reduce serotonin levels in the synaptic cleft, may cause or contribute to the increase in 5-HT 1B receptor binding in the SCN in middle aged animals. These results show that the SCN exhibits changes in serotonergic function during middle age, which has been characterized by changes in the expression of circadian rhythms. Because these changes occur during middle age, they probably reflect the aging process, rather than senescence or disease. 相似文献
15.
5-Hydroxytryptamine (5-HT, serotonin), synthesized in midbrain raphe nuclei and released in various hypothalamic sites, decreases food intake but the specific 5-HT receptor subtypes involved are controversial. Here, we have studied changes in the regional density of binding to 5-HT receptors and transporters and the levels of tryptophan hydroxylase, in rats with obesity induced by feeding a palatable high-energy diet for 7 weeks. We mapped binding at 5-HT receptor subtypes and transporters using quantitative autoradiography and determined tryptophan hydroxylase protein levels by Western blotting. In diet-induced obese (DiO) rats, specific binding to 5-HT 1A receptors ([ 3H]8-OH-DPAT) was significantly increased in the dorsal and median raphe by 90% ( P<0.01) and 132% ( P<0.05), respectively, compared with chow-fed controls. 5-HT 1B receptor binding sites ([ 125I]cyanopindolol) were significantly increased in the hypothalamic arcuate nucleus (ARC) of DiO rats (58%; P<0.05), as were 5-HT 2A receptor binding sites ([ 3H]ketanserin) in both the ARC (44%; P<0.05) and lateral hypothalamic area (LHA) (121%; P<0.05). However, binding to 5-HT 2C receptors ([ 3H]mesulgergine) in DiO rats was not significantly different from that in controls in any hypothalamic region. Binding to 5-HT transporters ([ 3H]paroxetine) was significantly increased ( P<0.05) in both dorsal and median raphe, paraventricular nuclei (PVN), ventromedial nuclei (VMH), anterior hypothalamic area (AHA) and LHA of DiO rats, by 47%–165%. Tryptophan hydroxylase protein levels in the raphe nuclei were not significantly different between controls and DiO rats. In conclusion, we have demonstrated regionally specific changes in binding to certain 5-HT receptor subtypes in obesity induced by voluntary overeating of a palatable diet. Overall, these changes are consistent with reduced 5-HT release and decreased activity of the 5-HT neurons. Reduction in the hypophagic action of 5-HT, possibly acting at 5-HT 1A, 5-HT 1B and 5-HT 2A receptors, may contribute to increased appetite in rats presented with highly palatable diet. 相似文献
16.
A single exposure to the elevated plus-maze test (EPM) increases open arms avoidance and reduces or abolishes the anxiolytic-like effect of benzodiazepines assessed during a second trial, a phenomenon defined as “one-trial tolerance” (OTT). It has been emphasized that the dorsal portion of the midbrain periaqueductal gray (dPAG) plays a role on this enhanced aversion phenomenon in maze-experienced rodents. Given that intra-dPAG injections of a wide range of serotonergic 5-HT 1A, 5-HT 2A and 5-HT 2C receptor agonists produce anxiolytic-like effects in maze-naïve rodents, the present study examined the effects of the 5-HT 1A receptor agonist 8-OH-DPAT (5.6 and 10.0 nmol in 0.15 µl) the preferential 5-HT 2A receptor agonist DOI (2.0 and 8.0 nmol in 0.1 µl) and the preferential 5-HT 2C receptor agonist MK-212 (21.2 and 63.6 nmol in 0.1 µl) microinjected into the dPAG prior to Trial 1 and Trial 2 on the behaviour of mice in the EPM. Test sessions were recorded and subsequently scored for anxiety-like behaviour (percentage of open arms entries and time) as well as general locomotor activity (closed arm entries). The results showed a lack of 8-OH-DPAT (5.6 and 10.0 nmol) effect on the behaviour of maze-naïve and maze-experienced mice, while intra-dPAG microinfusions of DOI (8 nmol) reduced anxiety-like behaviour only in maze-experienced mice that had received a similar treatment prior to Trial 1. Furthermore, intra-dPAG MK-212 (63.6 nmol) showed an anxiolytic-like effect on both Trial 1 and Trial 2. Importantly, these effects were observed in the absence of any significant change in closed arm entries, the parameter considered to be a valid index of locomotor activity in the plus-maze. These results support the dPAG as a crucial structure involved in the neurobiology of the OTT phenomenon as well as accounting the role of the 5-HT 2A and 5-HT 2C receptors located within this midbrain structure on the emotional state induced by EPM test and retest paradigm mice. 相似文献
17.
Maternal separation is known to induce long-term changes in neuroendocrine and emotional responsiveness to stress in a large variety of models. We examined an animal model of early deprivation in Sprague–Dawley rats consisting of separating litters from their mothers and littermates 3 h daily during postnatal days 2 to 15. In adulthood, maternally deprived rats in comparison with non-deprived controls exhibited an increase in anxiety and depression-related behaviors in the open-field and forced swim tests. Because serotonin (5-HT) 5-HT 1A receptors seem to play an important role in the pathophysiology of major depression and in the mechanism of action of antidepressants, we investigated if 5-HT 1A receptor function is altered in deprived rats. Although the hypothermic response to the 5-HT 1A receptor agonist 8-OH-DPAT was increased in adult deprived rats compared to non-deprived control group, no differences between groups were found in the effect of the systemic 8-OH-DPAT administration on serotoninergic cell firing in dorsal raphe nucleus and in the 5-HT release at the ventral hippocampus levels. These results suggest that 5-HT 1A receptors are not substantially affected in adult Sprague–Dawley rats that were subjected to a maternal deprivation 3 h daily during the neonatal period. 相似文献
18.
Estrogen deficiency has been associated with stress, anxiety and depression. Estrogen receptors have been identified in the median raphe nucleus (MRN). This structure is the main source of serotonergic projections to the hippocampus, a forebrain area implicated in the regulation of defensive responses and in the resistance to chronic stress. There is reported evidence indicating that estrogen modulates 5-HT 1A receptor function. In the MRN, somatodendritic 5-HT 1A receptors control the activity of serotonergic neurones by negative feedback. The present study has evaluated the effect of intra-MRN injection of estradiol benzoate (EB, 600 or 1200 ng/0.2 μl) on the performance of ovariectomized rats submitted to contextual conditioning. Additionally, the same treatment was given after intra-MRN injection of Way 100635 (100 ng/0.2 μl), a 5-HT 1A receptor antagonist. Both doses of EB decreased freezing and increased rearing, indicating an anxiolytic effect. Pretreatment with Way 100635 antagonized the anxiolytic effect of estradiol. On the basis of these results, it may be suggested that estrogens modulate anxiety by acting on 5-HT 1A receptors localized in the MRN. 相似文献
19.
Summary. Radioligand binding studies were done to investigate the effect of chronic administration of fluoxetine on 5-HT 1 receptor mediated response to adenylate cyclase (AC) in rat brain. Our studies revealed a significant decrease in the densities
of 5-HT 1 and 5-HT 1A receptor sites in cortex and hippocampus of rat brain after chronic administration of fluoxetine (10 mg/Kg body wt.). However
there was no significant change in the affinity of [ 3H]5-HT and [ 3H]DPAT for 5-HT 1 and 5-HT 1A receptor sites, respectively. However, in striatum, along with a significant (75%) downregulation of 5-HT 1 sites, the affinity of [ 3H]5-HT to these sites was increased, as revealed by decrease in Kd (0.50 ± 0.08 nM). Displacement studies showed that fluoxetine
has higher affinity for 5-HT 1A receptors with a Ki value of 14.0 ± 2.8 nM, than 5-HT 1 sites. No significant change was observed in basal AC activity in any region after fluoxetine exposure. However, in cortex
of experimental rats the 5-HT stimulated AC activity was significantly increased (16.03 ± 0.97 pmoles/mg protein; p < 0.01),
when compared to 5-HT stimulated AC activity (12.98 ± 0.78 pmoles/mg protein) in control rats. The increase in 5-HT stimulated
AC activity in cortex may be due to the significant downregulation of 5-HT 1A sites in cortex after fluoxetine exposure as these sites are negatively coupled to AC. The observed significant decrease
in 5-HT 1 sites with concomitant increase in 5-HT stimulated AC activity, after fluoxetine treatment, suggests that fluoxetine, which
has high affinity for these sites, acts by modulating the 5-HT 1A receptor mediated response in brain.
Accepted August 25, 1999 相似文献
20.
Antisocial behavior (ASB) is characterized by frequent violations of the rights and properties of others, as well as aggressive conduct. While ample evidence points to a critical role of serotonin in the emotional modulation of social responses, the implication of this neurotransmitter in ASB is unclear. Here, we performed the first-ever postmortem analysis of serotonergic markers in the orbitofrontal cortex (OFC) of male subjects with ASB (n = 9). We focused on this brain region, given its well-recognized role in social response and ASB pathophysiology. Given that all individuals also had a substance use disorder (SUD) diagnosis, two age-matched control groups were used: SUD only and unaffected controls. Tissues were processed for immunoblotting analyses on eight key serotonergic targets: tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of brain serotonin synthesis; serotonin transporter (SERT), the primary carrier for serotonin uptake; monoamine oxidase A (MAOA), the primary enzyme for serotonin catabolism; and five serotonin receptors previously shown to influence social behavior: 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4. Our analyses documented a significant increase in 5-HT2A receptor levels in the ASB + SUD group compared to SUD-only controls. Furthermore, TPH2 levels were significantly reduced in the SUD group (including SUD only and ASB + SUD) compared to unaffected controls. No difference was detected in the expression of any other serotonergic target. These results are in keeping with previous evidence showing high 5-HT2A receptor binding in the OFC of pathologically aggressive individuals and point to this molecule as a potential target for ASB treatment. 相似文献
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