Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity.

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33 ± 4.7 and -31 ± 5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35 ± 5.4 and -31 ± 5.5%, respectively, with an increase in blood pressure +26.3 ± 2.5; 3 mg/kg sertraline reduced RSNA by -59.4 ± 8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

Loss of cerebral white matter structural integrity tracks the gray matter metabolic decline in normal aging.

Relationships between structural MRI-based markers of declining cerebral integrity, and regional PET measurements of (18)FDG uptake have not been studied well in normal aging. In this manuscript we relate changes in cerebral morphology to regional cerebral glucose uptake for 14 major cortical areas in 19 healthy older individuals (age 59-92 years). Measurements of cerebral integrity included gray matter (GM) thickness, sulcal and intergyral spans, fractional anisotropy (FA) of water diffusion and volume of hyperintense WM (HWM) lesions. (18)FDG-PET measurements were converted to standard uptake values and corrected for partial volume artifact. Following this, cortical FDG uptake was significantly correlated with several indices of WM integrity that we previously observed to be sensitive to cognitive decline in executive function, including intergyral span and HWM volumes. Our findings suggest that the age-related decline in white matter integrity, observed as increases in HWM lesions, intergyral spans and reduction in FA, correlated with a decline in the global and regional cerebral glucose uptake. Our findings support the emerging consensus that WM integrity indices are sensitive predictors of declining cerebral health in normal aging. Specifically, age-related WM degradation in the thinly myelinated association tracts appears to track the decreases in global and regional rates of glucose uptake.

Investigation of the role of 5-HT2 receptor subtypes in the control of the bladder and the urethra in the anaesthetized female rat.

BACKGROUND AND PURPOSE: Micturition is controlled by central 5-HT-containing pathways. 5-HT2 receptors have been implicated in this system especially in control of the urethra, which is a drug target for treating urinary incontinence. This study investigates the role of each of the three subtypes of this receptor with emphasis on sphincter regulation. EXPERIMENTAL APPROACH: Recordings of urethral and bladder pressure, external urethral sphincter (EUS) EMG, as well as the micturition reflex induced by bladder distension along with blood pressure and heart rate were made in anaesthetized rats. The effects of agonists and antagonists for 5-HT2 receptor subtypes were studied on these variables. KEY RESULTS: The 5-HT2C agonists Ro 60-0175, WAY 161503 and mCPP, i.v., activated the EUS, increased urethral pressure and inhibited the micturition reflex. The effects of Ro 60-0175 on the EUS were blocked by the 5-HT2C antagonist SB 242084 and the 5-HT2A antagonists, ketanserin and MDL 100907. SB 242084 also blocked the inhibitory action on the reflex, while the 5-HT2B antagonist RS 127445 only blocked the increase in urethral pressure. The 5-HT2A receptor agonist DOI given i.v. or i.t. but not i.c.v. activated the EUS. CONCLUSIONS AND IMPLICATIONS: 5-HT2A/2C receptors located in the sacral spinal cord activate the EUS, while central 5-HT2C receptors inhibit the micturition reflex and 5-HT2B receptors, probably at the level of the urethra, increase urethral smooth muscle tone. Furthermore, 5-HT2B and 5-HT2C receptors do not seem to play an important role in the physiological regulation of micturition.

Cardiovascular effects of activation of central alpha7 and alpha4beta2 nAChRs: a role for vasopressin in anaesthetized rats.

BACKGROUND AND PURPOSE: Central application of nicotine causes the release of vasopressin and affects blood pressure. Involvement of the 5 neuronal nicotinic receptor groups, alpha2(*)-alpha7(*) in these effects is unknown. The availability of selective agonists for alpha7 (PSAB-OFP) and alpha4beta2 (TC-2559) nACh receptors allowed their role to be investigated. EXPERIMENTAL APPROACH: Recordings were made of arterial blood pressure, heart rate and renal sympathetic nerve activity in anaesthetized male rats with neuromuscular blockade and artificial respiration. Effects of the agonists, PSAB-OFP (1-10 micromol kg(-1)) and TC-2559 (1-10 micromol kg(-1)) on these variables given intracerebroventricularly (i.c.v.) and intracisternally (i.c.) in the presence or absence of the antagonists, DhbetaE (10 micromol kg(-1)) and MLA (0.5 micromol kg(-1)), for the appropriate nicotinic receptor subtypes, respectively, and a V(1) receptor antagonist, given i.v. or centrally, were investigated. KEY RESULTS: Both agonists given i.c.v. caused a delayed rise in blood pressure and renal nerve activity which could be blocked only with the appropriate antagonist. The agonists had an earlier onset of action when given i.c., favouring the brainstem as the major site of action. The effects of these agonists were also attenuated by the V(1) receptor antagonist given i.v. and blocked when this antagonist was given centrally. Antagonists had no effect on baseline variables. CONCLUSIONS AND IMPLICATIONS: Activation of alpha4beta2 and alpha7 receptors in the brainstem is mainly responsible for the cardiovascular effects of activating these receptors, which have a similar profile of action. These actions, although independent, are mediated by the central release of vasopressin.

Activation of 5-HT1B and 5-HT1D receptors in the rat nucleus tractus solitarius: opposing action on neurones that receive an excitatory vagal C-fibre afferent input.

BACKGROUND AND PURPOSE: Central 5-HT-containing pathways are known to be important in cardiovascular regulation and a crucial area for this regulation is the nucleus tractus solitarius (NTS), which contains many of the known 5-HT receptor subtypes. In this study the role of 5-HT(1B) and 5-HT(1D) receptors, targets for the antimigraine drugs known collectively as triptans, was examined in the NTS. EXPERIMENT APPROACH: Extracellular recordings were made, in anaesthetized rats, from 109 NTS neurones that were excited by electrical stimulation of the vagus and drugs were applied ionophoretically to these neurones. KEY RESULTS: The 5-HT(1B/1D) receptor agonist sumatriptan applied to 64 neurones produced a 64% reduction in the firing rate of 54 of these neurones. Ketanserin, a 5-HT(1D/2A) receptor antagonist, alone had little effect, but co-applied with sumatriptan significantly attenuated this inhibition, whilst co-application of the 5-HT(1B) receptor antagonist GR55562 resulted in potentiation of this inhibition. Sumatriptan also caused a 25% reduction in vagal afferent evoked activity as well as that caused by stimulation of cardiopulmonary afferents. In another 41 neurones the 5-HT(1B) receptor agonist CP-93 129 produced a doubling of the background firing rate in 31 of these neurones and a significant increase in both vagal afferent evoked activity and that evoked by cardiopulmonary afferent activation. CONCLUSIONS AND IMPLICATIONS: Activation of 5-HT(1B) and 5-HT(1D) receptors have opposing actions on NTS neurones of excitation and inhibition, respectively. As both receptors are negatively coupled to adenylate cyclase this would indicate that they have different anatomical locations within NTS.

Hypertrophic cardiomyopathy with shared morphology in identical twins: a case report.

We report the case of identical twin sisters, both with hypertrophic cardiomyopathy, and both found to have similar echocardiographic appearances in the form of asymmetric septal hypertrophy. This is unusual, in that published reports commonly describe the heterogeneous expression of this condition in twins.

Central cardiovascular regulation and 5-hydroxytryptamine receptors.

Evidence is provided to support the view that central 5-HT(1A) and 5-HT(2) receptors are the major receptor subtypes important in cardiovascular regulation. Data are also provided to implicate 5-HT(1B/1D/1F) receptors in central cardiovascular regulation. Activation of 5-HT(2) receptors generally causes sympathoexcitation and a rise in blood pressure and this is mainly mediated by 5-HT(2A) receptors. However, presympathetic vasomotor neurones located in the hindbrain (RVLM), controlling sympathetic outflow to the heart, are not activated in the same way as other presympathetic vasomotor neurones, although activation of 5-HT(2) receptors located in the midbrain can activate sympathetic outflow to the heart. Furthermore, at least in the rat, these midbrain 5-HT(2A) receptors are also responsible for the release of vasopressin by activation of a central angiotensinergic pathway. The ability of vasopressin directly and/or indirectly to modify renal sympathetic outflow involves the activation of central 5-HT(2B) receptors, which in turn, when activated via the i.c.v. route, can cause selective renal sympathoexcitation. Evidence is also provided which indicates that the reflex control of parasympathetic outflow to the heart and to other organs involves central 5-HT(1A) receptors located in the vicinity of these preganglionic vagal neurones. Finally, 5-HT(3) receptors are implicated in the afferent regulation of central sympathetic and parasympathetic tone.

The role of central 5-HT(1A) receptors in the control of B-fibre cardiac and bronchoconstrictor vagal preganglionic neurones in anaesthetized cats.

1. Experiments were performed to determine whether 5-HT(1A) receptors (a) modulate the activity of cardiac and bronchoconstrictor vagal preganglionic neurones (CVPNs and BVPNs) in the nucleus ambiguus (NA) and (b) are involved in pulmonary C-fibre afferent-evoked excitation of CVPNs, by right-atrial injections of phenylbiguanide (PBG). These experiments were carried out on alpha-chloralose-anaesthetized, artificially ventilated and atenolol (1 mg kg(-1))-pretreated cats. 2. The ionophoretic application of 8-OH-DPAT (a selective 5-HT(1A) receptor agonist) influenced the activity of 16 of the 19 CVPNs tested. 8-OH-DPAT tended to cause inhibition at low currents (40 nA) and excitation at high currents (120 nA). The activity of 15 of these neurones increased in response to the application of 8-OH-DPAT. In six of the CVPNs tested, this excitatory action of 8-OH-DPAT was attenuated by co-application of the selective 5-HT(1A) receptor antagonist WAY-100635. 3. The pulmonary C-fibre afferent-evoked excitation of eight CVPNs was attenuated by ionophoretic application of WAY-100635. 4. In three out of four CVPNs, the ionophoretic application of PBG caused excitation. 5. In five out of the nine identified BVPNs that were tested with ionophoretic application of 8-OH-DPAT, excitation was observed that was attenuated by WAY-100635. 6. WAY-100635 (I.V. or intra-cisternally) also reversed bradycardia, hypotension and the decrease in phrenic nerve activity evoked by the I.V. application of 8-OH-DPAT (42 microg kg(-1)). 7. In conclusion, the data indicate that 5-HT(1A) receptors located in the NA play an important role in the reflex activation of CVPNs and BVPNs, and support the view that overall, these receptors play a fundamental role in the reflex regulation of parasympathetic outflow.

Enoxaparin for thromboprophylaxis after major trauma: potential cost implications.

OBJECTIVE: To determine the cost-effectiveness of enoxaparin compared with low-dose-heparin (LDH) for thromboprophylaxis after major trauma and to assess the economic significance of major bleeding as a complication of the use of low-molecular-weight heparin (LMWH). DESIGN: Decision model analysis of the cost and efficacy of enoxaparin at preventing venous thromboembolism (VTE) and the risk and costs of major hemorrhage related to LMWH. The primary outcome was deep vein thromboses (DVTs) averted. Model estimates were based on data from prospective trials of LMWH and other studies of the financial ramifications of DVT and pulmonary embolism. SETTING AND PATIENTS: Hypothetical cohort of 1,000 critically ill trauma patients requiring thromboprophylaxis. INTERVENTIONS: In the model, patients were managed with either LMWH or LDH. MEASUREMENTS AND MAIN RESULTS: The marginal cost-effectiveness of enoxaparin was calculated as the savings resulting from cases of DVT averted less the additional costs of both 1) LMWH and 2) major bleeding. This result is expressed as cost (or savings) per DVT prevented. Sensitivity analysis of the impact of the major clinical inputs on the cost-effectiveness was performed. The base case assumed that the incidence of DVT with LDH was 14.7%, that LMWH resulted in a relative risk reduction of DVT of 50%, but that enoxaparin nearly quadrupled the risk of bleeding. Despite the higher costs of enoxaparin, this tactic yielded a net savings of $391.23 per DVT prevented. For sensitivity analysis, model inputs were adjusted by 25% individually and then simultaneously. This demonstrated the model to be most sensitive to the calculated cost of a DVT. With the efficacy of LMWH reduced by 25% of the base-case estimate, enoxaparin resulted in a cost of $311.77 per DVT avoided. When all variables were skewed against LMWH, total outlays were trivial (approximately $85 per patient in the cohort). Neither the rate of increased bleeding with LMWH nor the costs incurred as a result of bleeding significantly altered the model's financial outcomes. CONCLUSIONS: Reliance on enoxaparin represents a strategy for the prevention of VTE after trauma that may result in savings. Neither concerns about the higher cost of enoxaprin relative to LDH nor the financial implications of major bleeding should preclude the use of LWMH for thromboprophylaxis in trauma patients. Further studies are warranted to confirm the efficacy of enoxaparin.

Memory impairments in adults with neurogenic communication disorders.

Over the past few decades, there has been increasing interest in the nonlinguistic, cognitive abilities of adults with neurogenic communication disorders. In particular, a growing literature has documented deficits in a number of memory functions in this population. The purpose of this article is to summarize that literature and provide an overview of the presence and nature of memory impairments in aphasia, right hemisphere disorders, traumatic brain injury, and dementia. Ways that memory impairments may interact with the communication abilities of individuals with neurogenic communication disorders also are discussed.

The role of alpha(1)-adrenoceptors and 5-HT(1A) receptors in the control of the micturition reflex in male anaesthetized rats.

1. The effects of the alpha(1)-adrenoceptor antagonists doxazosin (0.1 -- 2 mg kg(-1)), RS-100329 (alpha(1A); 0.01 -- 1 mg kg(-1)), RS-513815 (Ro 151-3815, alpha(1B); 0.3 -- 3 mg kg(-1)) and BMY 7378 (alpha(1D); 0.1 -- 1 mg kg(-1)), the 5-HT(1A) receptor agonist, 8-OH-DPAT (0.03 -- 0.3 mg kg(-1)) and antagonist WAY-100635 (0.03 -- 0.3 mg kg(-1)) were investigated (i.v.) on the 'micturition reflex' in the urethane anaesthetized male rat. 2. Reflex-evoked urethra contractions were most sensitive to the inhibitory action of RS-100329, followed by doxazosin, BMY 7378 and WAY-100635 and then RS-513815. The maximum inhibition was 66, 63, 54, 46 and 22% at doses of 0.3, 0.5, 0.3, 0.3 and 3 mg kg(-1) respectively. 3. BMY 7378 and 8-OH-DPAT decreased, while WAY-100635 increased, the pressure threshold to induce bladder contraction. WAY-100635 (0.01 mg kg(-1)) blocked the effects of BMY 7378 (1 mg kg(-1)) on bladder pressure and volume threshold. 4. Doxazosin, RS-100329 and BMY 7378 had a similar potency in inducing a fall in arterial blood pressure while WAY-100635 only caused a fall at the highest dose. 5. Therefore, reflex-evoked urethral contraction involves the activation of alpha(1A/1D)-adrenoceptors, as BMY 7378 and RS-100329 are similarly potent in attenuating this effect. The ability of WAY-100635 to attenuate this contraction may suggest that 5-HT(1A) receptors are also involved. However, as this inhibition occurred at the highest dose of WAY-100635, which also caused a fall in arterial blood pressure; this effect is considered to be due to blockade of alpha(1)-adrenoceptors not 5-HT(1A) receptors. Nevertheless the initiation of the 'micturition reflex' involves the activation of 5-HT(1A) receptors.

In vivo modulation of nucleus tractus solitarius (NTS) neurones by activation of 5-hydroxytryptamine(2) receptors in rats.

In in vivo experiments, 5-hydroxytryptamine (5-HT) and (+/-)-2,5-dimethoxy-4-iodoamphetamine HCl (DOI), a 5-HT(2) receptor agonist, were applied by ionophoresis to rat nucleus tractus solitarius (NTS) neurones identified by their vagal and cardiopulmonary afferent inputs to test whether the response of NTS cells to 5-HT(2) receptor activation was related to whether they received mono- or polysynaptic vagal inputs and their presumed function as defined by their afferent input. Cells were classified on the basis of the variability of the latency of the vagal-evoked spikes: this varied by less than 3 ms for Group 1, from 3 to 5 ms for Group 2, and more than 5 ms for Group 3. Both 5-HT and DOI inhibited most Group 1 cells (16/18) and inactive (without ongoing activity) cells (8/13) in Group 2. Cells inhibited by DOI were also inhibited by cardiopulmonary afferent stimulation, evoked by atrial phenylbiguanide administration. By contrast, application of 5-HT and DOI excited the majority of Group 3 cells (14/19) and Group 2 with ongoing activity (7/9). Cells excited by DOI were also activated by cardiopulmonary stimulation. Both actions of DOI were reversed by application of ketanserin (n=15). In conclusion, these data demonstrate that activation of 5-HT(2) receptors in the NTS produces different effects dependent on whether the neurones received mono- or polysynaptic vagal input and their response to cardiopulmonary afferent stimulation.

Assessing the executive function abilities of adults with neurogenic communication disorders.

Whereas it is known that executive function abilities are often impaired in clients having neurogenic communication disorders, few assessments of this cognitive domain are available that consider the speech and language deficits of this population. This article provides an overview of current procedures for assessing executive functions including a discussion of team approaches to assessment, a review of currently available neuropsychological and functional tests of executive function abilities, as well as a critique of those assessment procedures. In addition, suggestions are provided for how best to use or modify appropriately current tests of executive functioning for clients having acquired speech and language disorders as a result of brain damage.

Effect of pulmonary C-fibre afferent stimulation on cardiac vagal neurones in the nucleus ambiguus in anaesthetized cats.

It has been demonstrated previously that the vagal bradycardia evoked by activation of pulmonary C-fibres is not respiratory modulated. Experiments were carried out in alpha-chloralose anaesthetized cats to determine if these cardiac vagal preganglionic neurones (CVPNs) in the nucleus ambiguus (NA), which have respiratory modulated activity, can be activated when pulmonary C-fibre afferents are stimulated by right atrial injections of phenylbiguanide (PBG). Eleven CVPNs with B-fibre axons in the right cardiac vagal branches were identified and found to be localized within or ventrolateral to the nucleus ambiguus. Ionophoretic application of a high current of dl-homocysteic acid (DLH) induced a vagally mediated bradycardia and hypotension in six of eight sites from which CVPNs were recorded. The activity of B-fibre CVPNs, whether spontaneous (n = 4) or induced by ionophoresis of DLH (n = 7) was respiratory modulated, firing perferentially during post-inspiration and stage 2 expiration. This activity also correlated with the rising phase of the arterial blood pressure wave consistent with these CVPNs receiving an arterial baroreceptor input. Right atrial injections of PBG excited nine of eleven CVPNs tested. In eight of these activated neurones the onset latency of the excitation was within the pulmonary circulation time, consistent with being activated only by pulmonary C-fibre afferents. In two neurones the PBG-evoked excitation still occurred when central inspiratory drive was inhibited, as indicated by the disappearance of phrenic nerve activity. In conclusion, B-fibre respiratory modulated CVPNs can be activated following stimulation of pulmonary C-fibre afferents.

Evidence that activation of central 5-HT(2B) receptors causes renal sympathoexcitation in anaesthetized rats.

The effects of injections i.c.v. of alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (BW723C86; 0.02 - 2 micromol kg(-1)), a 5-HT(2B) receptor agonist, on renal sympathetic and phrenic nerve activity, mean arterial blood pressure and heart rate were investigated in alpha-chloralose anaesthetized rats pretreated with a peripherally acting 5-HT(2) receptor antagonist. BW723C86 i.c.v. caused a dose-related increase in renal nerve activity reaching a maximum of 67+/-6%, which at the highest dose was associated with a small and maintained fall in mean arterial blood pressure of 7+/-3 mmHg. These changes were not associated with any significant changes in heart rate or phrenic nerve activity. BW723C86-evoked increases in renal nerve activity and hypotension were attenuated by pretreatment (i.c.v.) with SB204741 (300 nmol kg(-1); a 5-HT(2B) receptor antagonist) but not by the same dose (i.c.v.) of ketanserin (a 5-HT(2A) receptor antagonist) or RS102221 (a 5-HT(2C) receptor antagonist). None of these antagonists alone had any effect on the variables being measured. It is concluded that central 5-HT(2B) receptors may play a selective role in the control of sympathetic supply to the kidney, which could be important in the central mechanisms involved in blood volume regulation. British Journal of Pharmacology (2000) 129, 177 - 183

The dynamics of chromosome evolution in birds and mammals.

Comparative mapping, which compares the location of homologous genes in different species, is a powerful tool for studying genome evolution. Comparative maps suggest that rates of chromosomal change in mammals can vary from one to ten rearrangements per million years. On the basis of these rates we would expect 84 to 600 conserved segments in a chicken comparison with human or mouse. Here we build comparative maps between these species and estimate that numbers of conserved segments are in the lower part of this range. We conclude that the organization of the human genome is closer to that of the chicken than the mouse and by adding comparative mapping results from a range of vertebrates, we identify three possible phases of chromosome evolution. The relative stability of genomes such as those of the chicken and human will enable the reconstruction of maps of ancestral vertebrates.

Evidence for a role for central 5-HT2B as well as 5-HT2A receptors in cardiovascular regulation in anaesthetized rats.

1. The effects of injections i.c.v. of quipazine, (2 micromol kg-1) and 1-(2,5-di-methoxy-4-iodophenyl)-2-aminopropane (DOI; 2 micromol kg-1) on renal sympathetic and phrenic nerve activity, mean arterial blood pressure (MAP) and heart rate were investigated in alpha-chloralose anaesthetized rats pretreated with a peripherally acting 5-HT2 receptor antagonist. 2. Quipazine or DOI caused a rise in MAP which was associated with a tachycardia and renal sympathoinhibition in rats pretreated (i.c.v.) with the antagonist vehicle 10% PEG. These effects of quipazine were completely blocked by pretreatment with cinanserin (a 5-HT2 receptor antagonist) and attenuated by spiperone (a 5-HT2A receptor antagonist). However, pretreatment with SB200646A (a 5-HT2B/2C receptor antagonist) only blocked the sympathoinhibition, while pretreatment with SB204741 (a 5-HT2B receptor antagonist) reversed the sympathoinhibition to excitation as it also did for DOI. Quipazine also caused renal sympathoexcitation in the presence (i.v.) of a vasopressin V1 receptor antagonist. 3. Injection (i.v.) of the V1 receptor antagonist at the peak pressor response evoked by quipazine alone and in the presence of SB204741 caused an immediate fall in MAP. For quipazine alone the renal sympathoinhibition was slowly reversed to an excitation, while the renal sympathoexcitation observed in the presence of SB204741 was potentiated. In both, the quipazine-evoked tachycardia was unaffected. 4. The data indicate that cardiovascular responses caused by i.c.v. quipazine and DOI are primarily due to activation of central 5-HT2A receptors, which causes the release of vasopressin and a tachycardia. This released vasopressin appears to suppress a 5-HT2A receptor-evoked central increase in sympathetic outflow, which involves the activation of central 5-HT2B receptors indirectly by the released vasopressin.