Inadvertent injection of medetomidine in the cerebromedullaris cisterna of a dog during myelographic exam.

INTRODUCTION: A mixed breed dog was anesthetized for diagnostic myelography to investigate acute onset neck pain. Instead of contrast medium, 444 µg/kg medetomidine were inadvertently injected into the cerebromedullaris cisterna owing to a human error. Severe bradycardia, undetectable peripheral pulse, respiratory arrest and loss of pupillary, palpebral and corneal reflexes were observed immediately after injection. Profound hypothermia developed and esophageal temperature, measured 20 minutes after medetomidine injection, was 33 °C. Atipamezole at 1 mg/kg im was administered, followed by a second dose of 0,5 mg/kg iv 20 minutes thereafter. In the meantime, cardiorespiratory parameters and body temperature were monitored, and supportive care that included manually assisted pulmonary ventilation, active warming, and administration of 5 µg/kg/min dopamine was initiated. The dog's clinical condition improved within one hour from the beginning of supportive care, at which time ocular reflexes and swallowing returned, spontaneous ventilation was deemed as adequate and the trachea could be extubated. The dog was discharged in good clinical conditions five days later. Human error and distraction led to a potentially life-threatening complication in the dog of this report and could have possibly been prevented with the use of checklists and with a clearer definition of roles and responsibilities of the personnel involved prior to commencing the clinical procedure. Profound cardiovascular, respiratory, and thermoregulatory depression caused by intracisternal injection of medetomidine responded to parenteral administration of its antagonist and supportive care.

INTRODUCTION: Un chien croisé a été anesthésié pour une myélographie diagnostique afin d'étudier une douleur aiguë au niveau du cou. Au lieu du produit de contraste, 444 µg/kg de médétomidine ont été injectés par inadvertance dans la citerne cérébello-médullaire en raison d'une erreur humaine. Une bradycardie sévère, un pouls périphérique indétectable, un arrêt respiratoire et une perte des réflexes pupillaire, palpébral et cornéen ont été observés immédiatement après l'injection. Une hypothermie profonde s'est développée et la température oesophagienne, mesurée 20 minutes après l'injection de médétomidine, était de 33 °C. De l'atipamézole à 1 mg/kg im a été administré, suivi d'une seconde dose de 0,5 mg / kg iv 20 minutes après. Dans l'intervalle, les paramètres cardiorespiratoires et la température corporelle ont été surveillés et des soins de soutien comprenant une ventilation assistée manuellement, un réchauffement actif et l'administration de 5 µg/kg/min de dopamine ont été initiés. L'état clinique du chien s'est amélioré dans l'heure qui a suivi le début des soins, moment où les réflexes oculaires et la déglutition sont réapparus, la ventilation spontanée a été jugée adéquate et où on a pu procéder à l'extubation. Le chien est sorti dans de bonnes conditions cliniques cinq jours plus tard. Une erreur humaine et de la distraction ont conduit à une complication potentiellement mortelle chez le chien décrit dans ce rapport et auraient pu être évitées grâce à l'utilisation de listes de contrôle et avec une définition plus claire des rôles et des responsabilités du personnel impliqué avant le début de la procédure clinique. Une profonde dépression cardiovasculaire, respiratoire et de la thermorégulation causée par l'injection intracisternale de médétomidine a répondu à l'administration parentérale de son antagoniste et à des soins de soutien.

Dexmedetomidine attenuates sevoflurane­induced neurocognitive impairment through α2­adrenoceptors.

It has been reported that sevoflurane induces neurotoxicity in the developing brain. Dexmedetomidine is an α2 adrenoceptor agonist used for the prevention of sevoflurane­induced agitation in children in clinical practice. The aim of the present study was to determine whether dexmedetomidine could prevent sevoflurane­induced neuroapoptosis, neuroinflammation, oxidative stress and neurocognitive impairment. Additionally, the involvement of α2 adrenoceptors in the neuroprotective effect of dexmedetomidine was assessed. Postnatal day (P)6 C57BL/6 male mice were randomly divided into four groups (n=6 in each group). Mice were pretreated with dexmedetomidine, either alone or together with yohimbine, an α2 adrenoceptor inhibitor, then exposed to 3% sevoflurane in 25% oxygen. Control mice either received normal saline alone or with sevoflurane exposure. Following sevoflurane exposure, the expression of cleaved caspase­3 was detected by immunohistochemistry in hippocampal tissue sections. In addition, the levels of tumor necrosis factor­α (TNF­α), interleukin (IL)­1ß, IL­6 and malondialdehyde, as well as superoxide dismutase (SOD) activity in the hippocampus were measured. At P35, the learning and memory abilities were assessed in each mouse using a Morris water maze test. Dexmedetomidine significantly decreased the expression of activated caspase­3 following sevoflurane exposure. Moreover, dexmedetomidine significantly decreased the levels of TNF­α, IL­1ß and IL­6 in the hippocampus. SOD activity also increased in a dose­dependent manner in dexmedetomidine­treated mice. MDA decreased in a dose­dependent manner in dexmedetomidine­treated mice. Lastly, sevoflurane­induced learning and memory impairment was reversed by dexmedetomidine treatment. By contrast, co­administration of yohimbine significantly attenuated the neuroprotective effects of dexmedetomidine. These findings suggested that dexmedetomidine exerted a neuroprotective effect against sevoflurane­induced apoptosis, inflammation, oxidative stress and neurocognitive impairment, which was mediated, at least in part, by α2 adrenoceptors.

Total injectable anesthesia of dogs and cats for remote location veterinary sterilization clinic.

BACKGROUND: Sterilization clinics often occur in remote places where anesthesia machines and compressed oxygen are unavailable. This study describes the use of total injectable anesthesia in dogs and cats presented for sterilization in a remote location. RESULTS: A total of 100 animals were sterilized; 26 female cats (CF), 22 male cats (CM), 28 female dogs (DF), and 24 male dogs (DM). CF were anesthetized with dexmedetomidine (20 mcg/kg), ketamine (8 mg/kg) and hydromorphone (0.1 mg/kg) IM. CM were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. Insufficient anesthesia in cats was treated with alfaxalone (1 mg/kg) IM. All cats were administered meloxicam at 0.3 mg/kg SQ. DF were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (7-10 mg/kg) and hydromorphone (0.1 mg/kg) IM. DM were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. All dogs had IV catheter and endotracheal tube placed. If SpO2 < 91%, ventilation was assisted with an Ambu bag. Insufficient anesthesia in dogs was treated with alfaxalone (1 mg/kg) IV. All dogs were administered meloxicam at 0.2 mg/kg SQ. Following surgery, atipamezole (0.05-0.1 mg/kg) IM was administered to any patient that did not have voluntary movement. All patients survived and were discharged. Less than 25% of cats and male dogs required supplemental anesthesia. Fifty seven percent of female dogs required supplemental anesthesia. More than 89% of patients (in any group) required atipamezole administration. One cat recovered with agitation and hyperthermia (41.1C/ 106F). Some dogs required ventilatory assistance to remain normoxemic while anesthetized. CONCLUSION: Total injectable anesthesia can be accomplished for remote location sterilization clinics with minimal morbidity.

Mirtazapine, an α2 Antagonist-Type Antidepressant, Reverses Pain and Lack of Morphine Analgesia in Fibromyalgia-Like Mouse Models.

Treatment of fibromyalgia is an unmet medical need; however, its pathogenesis is still poorly understood. In a series of studies, we have demonstrated that some pharmacological treatments reverse generalized chronic pain but do not affect the lack of morphine analgesia in the intermittent cold stress (ICS)-induced fibromyalgia-like pain model in mice. Here we report that repeated intraperitoneal treatments with mirtazapine, which is presumed to disinhibit 5-hydroxytriptamine (5-HT) release and activate 5-HT1 receptor through mechanisms of blocking presynaptic adrenergic α2 and postsynaptic 5-HT2 and 5-HT3 receptors, completely reversed the chronic pain for more than 4 to 5 days after the cessation of treatments. The repeated mirtazapine treatments also recovered the morphine analgesia after the return of nociceptive threshold to the normal level. The microinjection of small interfering RNA (siRNA) adrenergic α2a receptor (ADRA2A) into the habenula, which showed a selective upregulation of α2 receptor gene expression after ICS, reversed the hyperalgesia but did not recover the morphine analgesia. However, both reversal of hyperalgesia and recovery of morphine analgesia were observed when siRNA ADRA2A was administered intracerebroventricularly. As the habenular is reported to be involved in the emotion/reward-related pain and hypoalgesia, these results suggest that mirtazapine could attenuate pain and/or augment hypoalgesia by blocking the habenular α2 receptor after ICS. The recovery of morphine analgesia in the ICS model, on the other hand, seems to be mediated through a blockade of α2 receptor in unidentified brain regions. SIGNIFICANCE STATEMENT: This study reports possible mechanisms underlying the complete reversal of hyperalgesia and recovery of morphine analgesia by mirtazapine, a unique antidepressant with adrenergic α2 and serotonergic receptor antagonist properties, in a type of intermittently repeated stress (ICS)-induced fibromyalgia-like pain model. Habenula, a brain region which is related to the control of emotional pain, was found to play key roles in the antihyperalgesia, whereas other brain regions appeared to be involved in the recovery of morphine analgesia in the ICS model.

Effects of atipamezole dosage and timing of administration on recovery time and quality in cats following injectable anaesthesia incorporating ketamine.

OBJECTIVES: The aim of this study was to establish the optimum dosage and timing of administration of atipamezole in cats undergoing general anaesthesia incorporating ketamine to provide the shortest recovery possible without unacceptably compromising recovery quality. METHODS: In total, 128 healthy male cats (age range 2-108 months, weight range 0.56-5.22 kg) admitted for castration were randomly allocated to groups of 32. Anaesthesia was induced with 60 mg/m2 ketamine, 180 µg/m2 buprenorphine, 3 mg/m2 midazolam and 600 µg/m2 medetomidine intramuscularly (IM). Cats received 600 µg/m2 (groups 1ATI20 and 1ATI40) or 1.5 mg/m2 (groups 2.5ATI20 and 2.5ATI40) atipamezole IM either 20 (groups 1ATI20 and 2.5ATI20) or 40 mins (groups 1ATI40 and 2.5ATI40) after the 'quad'. Preparation time, surgical time, auricular temperature, times to sternal recumbency and first standing, and recovery quality score were recorded. Data were analysed using ANOVA, Kruskal-Wallis, Mann-Whitney U-tests and χ2 tests. Statistical significance was deemed to be P ⩽0.05. RESULTS: Groups did not differ significantly in preparation or surgical time. Auricular temperature decreased significantly over time (P <0.01) but did not differ between atipamezole treatment groups. Time to sternal recumbency in group 2.5ATI20 (52.9 ± 22.3 mins) was faster than group 1ATI20 (65.7 ± 24.7 mins) (P ⩽0.05), but there were no significant differences between other groups. Time to first standing and recovery quality scores did not differ significantly between groups. Minimal adverse effects were seen. CONCLUSIONS AND RELEVANCE: Atipamezole administration after 20 mins did not reduce recovery time but neither was recovery quality adversely affected compared with when it was administered after 40 mins, following datasheet recommendations with concurrent ketamine administration. The results of this study also suggest that an atipamezole:medetomidine dose ratio of 2.5:1 is more effective than 1:1 in reducing recovery time, regardless of timing of administration, although this only reached statistical significance for time to sternal recumbency when atipamezole was administered after 20 mins.

What is the evidence for mirtazapine in treating cancer-related symptomatology? A systematic review.

PURPOSE: Cancer patients often experience multiple distressing symptoms which are challenging to manage. It would therefore be helpful to find a treatment that alleviates more than one symptom, to avoid polypharmacy: mirtazapine has been used in several studies for this purpose. The objective of this study was to assess the effectiveness and safety of mirtazapine in alleviating one or more frequently encountered cancer-related symptoms. METHODS: Systematic review of clinical trials in English or French. Eight databases were searched. Included studies assessed the effectiveness of mirtazapine in alleviating one or more frequently encountered cancer-related symptoms. Comparator and validated assessment tools were required. Studies were independently appraised by two investigators before data synthesis. RESULTS: The search yielded 1898 references, from which we identified 12 relevant articles evaluating highly heterogeneous outcomes. These were two randomised-controlled (RCTs), three non-randomised controlled, and seven non-randomised non-controlled trials. In total, 392 participants were included and 185 were in RCTs. No study assessed the effectiveness of mirtazapine in alleviating symptoms at the same time, but some considered more than one symptom. Overall, the data was of poor quality, limited by small sample size and bias. However, mirtazapine showed effectiveness in treating depression, anxiety, sleep disorders, emesis and neuropathic pain. Across all studies, mirtazapine is safe to use, with drowsiness and dizziness the most common side-effects. CONCLUSION: Study design and small sample sizes limit the ability to interpret results. Trials to assess the impact of mirtazapine or other medicines in alleviating multiple symptoms would be valuable.

Intratesticular and incisional line infiltration with ropivacaine for castration in medetomidine-butorphanol-midazolam sedated dogs.

OBJECTIVE: To evaluate whether intratesticular and incisional ropivacaine infiltration produces sufficient intra- and postoperative analgesia for castrating dogs under sedation. STUDY DESIGN: Randomized, blinded, controlled clinical study. ANIMALS: Twenty-three healthy dogs weighing 5.8-35.6 kg admitted for castration. METHODS: Dogs were sedated with medetomidine (0.01 mg kg-1), butorphanol (0.2 mg kg-1) and midazolam (0.2 mg kg-1) intramuscularly, and were randomly assigned to group R, 0.2-0.4 mL kg-1 of ropivacaine 0.5%, or group S, an equivalent volume of saline injected intratesticularly and along the incision line. If persistent motion was observed during surgery, sedation was considered to be insufficient and general anaesthesia was induced. Carprofen 2.2 mg kg-1 was administered postoperatively. Pain was evaluated in all dogs before sedation and postoperatively following atipamezole administration at 1, 2, 4, 8 and 24 hours using an interactive visual analogue scale (IVAS; 0-100), the Glasgow composite pain scale-short form (CMPS-SF; 0-24), and a mechanical algometer. Methadone 0.3 mg kg-1 was administered intravenously to dogs if IVAS >30 or CMPS-SF >4. RESULTS: There was no significant difference between groups for the number of dogs administered general anaesthesia. The time from the beginning of surgery to induction of general anaesthesia was significantly shorter [median (range)] in group S [6 (3-25) minutes] than in group R [56 (36-76) minutes]. At 8 hours IVAS was significantly higher in group S (14 ± 10) than in group R (6 ± 4). CONCLUSIONS AND CLINICAL RELEVANCE: Intratesticular and incisional ropivacaine infiltration delayed the time to anaesthesia induction, and provided analgesia after castration performed under deep sedation in dogs. Intratesticular local anaesthesia can be an important part of the anaesthetic plan for castration.

Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities.

Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1ß by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time.

Disruption of Spinal Noradrenergic Activation Delays Recovery of Acute Incision-Induced Hypersensitivity and Increases Spinal Glial Activation in the Rat.

UNLABELLED: Results of clinical studies suggest that descending inhibitory controls from the brainstem are important for speeding recovery from pain after surgery. We examined the effects of destroying spinally projecting noradrenergic neurons via intrathecally administered antibody to dopamine ß-hydroxylase conjugated to saporin (DßH-saporin) on recovery in an acute incisional pain model. Mechanical and thermal paw withdrawal thresholds and nonevoked spontaneous guarding scores were tested for several weeks postoperatively and analyzed using mixed effects growth curve modeling. DßH-saporin treatment resulted in a significant prolongation in the duration of mechanical and to a lesser degree thermal hypersensitivity in the ipsilateral paw of incised rats but did not increase the duration of spontaneous guarding. DßH-saporin treatment was also associated with increased microglial and astrocyte activation in the ipsilateral spinal cord 21 days after incision compared with immunoglobulin G-saporin treated controls. Chronic intrathecal administration of the α2 adrenergic receptor antagonist atipamezole (50-200 µg/d) produced similar effects. These data suggest that spinally projecting noradrenergic pathways and spinal α2 adrenergic receptor activation are important for speeding recovery from hypersensitivity after surgical incision possibly by reducing spinal glial activation. Interventions that augment the noradrenergic system might be important to speed recovery from pain after surgery. PERSPECTIVE: Endogenous descending spinal noradrenergic activation promotes resolution of incision-induced hypersensitivity and inhibits spinal microglial and astrocyte activation in part through α2 adrenergic receptors.

Usefulness of an anesthetic mixture of medetomidine, midazolam, and butorphanol in cotton rats (Sigmodn hispidus).

Tne cotton rat (Sigmodon hispidus) is a laboratory rodent used for studying human infectious diseases. However, a lack of suitable anesthetic agents inconveniences the use of cotton rats in surgical manipulation. This study demonstrated that subcutaneous injection of the mixture of medetomidine, midazolam, and butorphanol (0.15, 2.0, and 2.5 mg/kg, respectively), which is a suitable anesthetic agents for mice and rats, produced an anesthetic duration of more than 50 min in cotton rats. We also demonstrated that 0.15 mg/kg of atipamezole, an antagonist of medetomidine, produced a quick recovery from anesthesia in cotton rats. This indicated that the anesthetic mixture of medetomidine, midazolam, and butorphanol, functioned as a useful and effective anesthetic for short-term surgery in cotton rats.

Optimal perioperative medication utilization in patients having arterial intervention.

Perioperative medical management of patients undergoing carotid, aortic, or peripheral arterial procedures, both open and endovascular, should be optimized in all cases to achieve excellent outcomes. This particular patient population is often plagued with multiple comorbidities, primarily of the cardiovascular system, but frequently involving other systems. For this reason, management of these comorbidities is complex and should be carefully addressed in every patient throughout the surgical encounter, in many cases through a multidisciplinary approach. Most recently, the perioperative use of statins, antiplatelet agents, and ß-blockers have been scrutinized in the literature specifically targeting peripheral vascular disease patients, and results have sometimes been conflicting. The objective of this review is to summarize current available evidence regarding optimal perioperative medical management of patients undergoing arterial vascular surgical procedures, open and endovascular.

Detomidine and the combination of detomidine and MK-467, a peripheral alpha-2 adrenoceptor antagonist, as premedication in horses anaesthetized with isoflurane.

OBJECTIVE: To investigate MK-467 as part of premedication in horses anaesthetized with isoflurane. STUDY DESIGN: Experimental, crossover study with a 14 day wash-out period. ANIMALS: Seven healthy horses. METHODS: The horses received either detomidine (20 µg kg(-1) IV) and butorphanol (20 µg kg(-1) IV) alone (DET) or with MK-467 (200 µg kg(-1) IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg(-1) ) and midazolam (0.06 mg kg(-1) ) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2 ) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (Pa O2 /FiO2 ) and tissue oxygen delivery (DO2 ) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05. RESULTS: The induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and Pa O2 /FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller. CONCLUSIONS AND CLINICAL RELEVANCE: MK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP.

Role of the intraluminal contents and the continuity of intrinsic neurons in intracolonic capsaicin-induced contraction and defecation in dogs.

PURPOSE: We, herein, examined the role of the intraluminal contents and continuity of colonic intrinsic neurons in intracolonic capsaicin-induced enhancement of colonic motility and defecation. METHODS: Five beagle dogs were equipped with three strain gauge force transducers throughout the colon. The colonic contractile activity in response to intracolonic capsaicin was studied in intact dogs, dogs after colonic cleansing and dogs with transection/re-anastomosis (T/R) between the proximal and middle colon. The effects of intravenous yohimbine, a α2 adrenergic antagonist, on the colonic motility and defecation were also studied in the same models. RESULTS: In intact dogs, capsaicin (10 mg) and yohimbine (2 mg/kg) immediately induced contractions throughout the colon, with defecation occurring in all experiments. In dogs after colonic cleansing and T/R, the capsaicin (10 mg)-induced enhancement of colonic motility was decreased in the middle and distal colon, and capsaicin-induced defecation was observed in 0-20 % of experiments (p < 0.05 compared to intact dogs). The effect of yohimbine (2 mg/kg) in inducing colonic contractions was unaltered after colonic cleansing and T/R; in contrast, yohimbine-induced defecation was not observed after colonic cleansing, but was unchanged after T/R. CONCLUSIONS: The continuity of the colonic intrinsic nerves as well as the intraluminal contents appear to play an important role in the colonic motor response to intracolonic capsaicin.

Caffeine consumption prevents memory impairment, neuronal damage, and adenosine A2A receptors upregulation in the hippocampus of a rat model of sporadic dementia.

Intracerebroventricular (icv) streptozotocin (STZ) administration induces pathological and behavioral alterations similar to those observed in Alzheimer's disease (AD) and is thus considered an experimental model of sporadic AD. Since caffeine (an adenosine receptor antagonist) and selective antagonists of adenosine A2A receptors modify the course of memory impairment in different amyloid-ß-based experimental models of AD, we now tested the impact of caffeine on STZ-induced dementia and associated neurodegeneration in the hippocampus as well as on the expression and density of adenosine receptors. Adult male rats received a bilateral infusion of saline or STZ (3 mg/kg, icv), which triggered memory deficits after four weeks, as gauged by impaired object recognition memory. This was accompanied by a reduced NeuN immunoreactivity in the hippocampal CA1 region and an increased expression and density of adenosine A2A receptors (A2AR), but not A1R, in the hippocampus. Caffeine consumption (1 g/L in the drinking water starting 2 weeks before the STZ challenge) prevented the STZ-induced memory impairment and neurodegeneration as well as the upregulation of A2AR. These findings provide the first demonstration that caffeine prevents sporadic dementia and implicate the control of central A2AR as its likely mechanism of action.

The alpha2 adrenergic receptor antagonist idazoxan, but not the serotonin-2A receptor antagonist M100907, partially attenuated reward deficits associated with nicotine, but not amphetamine, withdrawal in rats.

Based on phenomenological similarities between anhedonia (reward deficits) associated with drug withdrawal and the negative symptoms of schizophrenia, we showed previously that the atypical antipsychotic clozapine attenuated reward deficits associated with psychostimulant withdrawal. Antagonism of alpha(2) adrenergic and 5-HT(2A) receptors may contribute to these effects of clozapine. We investigated here whether blockade of alpha(2) or 5-HT(2A) receptors by idazoxan and M100907, respectively, would reverse anhedonic aspects of psychostimulant withdrawal. Idazoxan treatment facilitated recovery from spontaneous nicotine, but not amphetamine, withdrawal by attenuating reward deficits and increase the number of somatic signs. Thus, alpha(2) adrenoceptor blockade may have beneficial effects against nicotine withdrawal and may be involved in the effects of clozapine previously observed. M100907 worsened the anhedonia associated with nicotine and amphetamine withdrawal, suggesting that monotherapy with M100907 may exacerbate the expression of the negative symptoms of schizophrenia or nicotine withdrawal symptoms in people, including schizophrenia patients, attempting to quit smoking.