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C T Dourish

Publications and source records attributed to C T Dourish.

At least 19 recordsLinked to original sources
PubMed2003

Oral administration of the 5-HT2Creceptor agonist, mCPP, reduces body weight gain in rats over 28 days as a result of maintained hypophagia.

RATIONALE: The 5-HT(2C) receptor subtype has been implicated extensively in the regulation of ingestive behaviour. OBJECTIVE: To assess whether chronic administration of the preferential 5-HT(2C) receptor agonist, mCPP, reduces rat body weight gain and to determine if this effect is wholly or partially attributable to the effect of the drug on daily food intake. METHODS: Animals were orally dosed with mCPP (10 mg/kg P.O., b.i.d.) or d-fenfluramine (2.5 mg/kg P.O., b.i.d.) for 28 days. Further groups of animals received drug treatments for the first 14 days and then received vehicle for the remainder of the experiment. Locomotor activity was assessed on days 2, 14, and 28. In a second study, animals received mCPP or d-fenfluramine for a 14-day period (dose and route were identical to the previous study). A group of pair-fed controls were included to determine whether the effects on body weight gain were attributable entirely to drug-induced hypophagia. RESULTS: Both mCPP and d-fenfluramine reduced body weight relative to vehicle-treated controls over the 28-day period. Withdrawal of the drugs on day 14 resulted in a significant rebound weight gain. Neither mCPP nor d-fenfluramine induced significant changes in locomotor activity compared to controls on any of the days tested (2, 14 or 28). In the second, 14-day study, changes in the body weights of pair-fed controls closely paralleled those of their drug-treated counterparts. CONCLUSION: These data indicate that chronic oral treatment with mCPP and d-fenfluramine significantly reduces rat body weight gain, an effect that is reversible upon withdrawal and wholly attributable to maintained hypophagia.

Administration, Oral↗
PubMed2003

Preferential effects of the cannabinoid CB1 receptor antagonist, SR 141716, on food intake and body weight gain of obese (fa/fa) compared to lean Zucker rats.

RATIONALE: The selective CB(1) receptor antagonist, SR 141716, has been demonstrated to reduce food consumption in a range of animal species. OBJECTIVE: To assess the effect of chronic administration of SR 141716 on body weight and ingestive behaviour of lean and obese (fa/fa) Zucker rats. METHODS: Lean and obese Zucker rats were orally dosed with SR 141716 (3, 10, 30 mg/kg PO), sibutramine (5 mg/kg PO) or vehicle for one week. Pair-fed controls provided insight as to whether the effect of SR 141716 on body weight was attributable to drug-induced hypophagia. Subsequently, the effect of chronic oral administration of SR 141716 (1, 3, 10 mg/kg) was assessed for 28 days. At the end of this period, all animals were given vehicle for 14 days. The incidence of wet-dog shakes, yawning, scratching, and grooming behaviours, was assessed after acute administration and at weekly intervals thereafter for 4 weeks. RESULTS: SR 141716 dose-dependently decreased food intake and body weight gain in both lean and obese animals. The inhibition of food intake and body weight gain was greater in obese Zuckers than in lean Zucker controls. Changes in the body weights of pair-fed controls closely paralleled those of their drug-treated counterparts. Chronic 28-day treatment led to a maintained reduction of body weight gain. Withdrawal of SR 141716 on day 28 resulted in rebound hyperphagia and a significant weight gain. On acute administration, SR 141716 dose-dependently induced motor behaviours that showed tolerance upon repeated administration. CONCLUSION: These data indicate that chronic oral treatment with SR 141716 significantly reduces the food intake and body weight gain of obese and lean Zucker rats, an effect that is greater in obese animals and reversible upon drug withdrawal.

Animals↗
PubMed2001

Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors.

The present series of studies is the first to investigate the pharmacological mechanisms underlying d-fenfluramine- and d-norfenfluramine-induced hypophagia in the rat using highly selective serotonin 5-HT2 receptor antagonists. Administration of d-fenfluramine, and its major metabolite d-norfenfluramine, suppresses food intake in animals. Both compounds stimulate the release of serotonin and are potent inhibitors of the re-uptake of 5-HT into nerve terminals. In addition, d-norfenfluramine also acts as a direct 5-HT(2B/2C) receptor agonist. Pre-treatment with the selective 5-HT2C receptor antagonist, SB-242084 (0.3-3 mg/kg), dose-dependently inhibited both d-fenfluramine- (3 mg/kg) and d-norfenfluramine-induced (2 mg/kg) hypophagia. In contrast, the hypophagic effect of d-fenfluramine and d-norfenfluramine was unaffected by prior treatment with the highly selective 5-HT2B receptor antagonists, SB-215505 (0.3-3 mg/kg) and RS-127445 (1-3 mg/kg) or the 5-HT2A receptor antagonists MDL 100,907 (0.003-0.03 mg/kg) and ketanserin (0.2, 0.5 mg/kg). In addition, the 5-HT1A receptor antagonist WAY-100635 (0.3, 1 mg/kg) and the 5-HT1B receptor antagonists GR-127935 (1, 2 mg/kg) and SB-224289 (2-10 mg/kg) did not affect d-fenfluramine-induced hypophagia. These data provide unequivocal evidence for an important role of the 5-HT2C receptor in the mediation of d-fenfluramine and d-norfenfluramine-induced hypophagia in the rat and do not support the involvement of 5-HT1A/1B/2A/2B receptors.

Animals↗
PubMed2001

Case series: amantadine open-label treatment of impulsive and aggressive behavior in hospitalized children with developmental disabilities.

OBJECTIVE: A growing body of literature implicates interactions between glutamatergic and neostriatal dopaminergic neurotransmitter systems in the development and expression of impulsivity, hyperactivity, and stereotypy. Amantadine hydrochloride, a drug used in young children for influenza prophylaxis, acts both as an indirect dopamine agonist as well as an N-methyl-D-aspartate (NMDA) receptor antagonist. Thus an open clinical trial of this medication for the treatment of symptoms of impulse control disorders in children was performed. METHOD: A total of eight children (seven with neurodevelopmental disorders and all inpatients) with target behaviors refractory to other treatments were selected after parental informed consent. All patients were male and ranged in age from 4 to 12 years. Outcome was based on subjective consensus clinical ratings by the multidisciplinary treatment team. RESULTS: For four of the children, amantadine was associated with marked clinical improvement. In the remainder, improvement was also observed. Amantadine was well tolerated. CONCLUSIONS: On the basis of this experience, it appears that amantadine hydrochloride or related NMDA antagonists may warrant additional study in this and related populations.

Aggression↗
PubMed2001

Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder.

OBJECTIVE: To test the hypothesis that amantadine hydrochloride is a safe and effective treatment for behavioral disturbances--for example, hyperactivity and irritability--in children with autism. METHOD: Thirty-nine subjects (intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavior Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI) scale were used as outcome variables. After a 1-week, single-blind placebo run-in, patients received a single daily dose of amantadine (2.5 mg/kg per day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day) for the subsequent 3 weeks. RESULTS: When assessed on the basis of parent-rated ABC-CV ratings of irritability and hyperactivity, the mean placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in absolute changes in clinician-rated ABC-CVs for hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated. CONCLUSIONS: Parents did not report statistically significant behavioral change with amantadine. However, clinician-rated improvements in behavioral ratings following treatment with amantadine suggest that further studies with this or other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must take into account the possibility of a large placebo response.

Adolescent↗
PubMed2000

Similarities in the action of Ro 60-0175, a 5-HT2C receptor agonist and d-fenfluramine on feeding patterns in the rat.

RATIONALE: Activation of 5-HT2C receptors is thought to enhance satiety and to mediate the action of the prototypical anorectic drug d-fenfluramine. OBJECTIVE: Four experiments investigated the role of the 5-HT2C receptor in the modulation of feeding by comparison of the effects of the putative selective 5-HT2C receptor agonist Ro 60-0175 and d-fenfluramine on feeding behaviour. METHODS: Microstructural analyses of meal patterning and drinking of a palatable solution were made over a range of drug doses administered to male Lister hooded rats. RESULTS: Ro 60-0175 increased the latency to the first meal (3 mg/kg) and reduced meal size (1 mg/kg). d-Fenfluramine (1 mg/kg) produced a similar behavioural pattern, but 3 mg/kg produced a more profound hypophagia that persisted for 10-12 h. Ro 60-0175 (1, 3 mg/kg) and d-fenfluramine (1.5 mg/kg) reduced ingestion of a palatable glucose/saccharin solution, by a reduction in the number of bouts of licking, with little effect on the size of individual bouts. d-Fenfluramine-induced hypophagia (2.1 mg/kg) was challenged by the administration of the selective 5-HT2C receptor antagonist SB 242084 (1, 3 mg/kg) in the meal patterning paradigm. SB 242084 significantly attenuated the decrease in feeding rate and increase in latency to feed produced by d-fenfluramine, but had no effect on the fenfluramine-induced reduction in meal size. A similar pattern of results was obtained when Ro 60-0175-induced hypophagia (3 mg/kg) was challenged by SB 242084 (1, 3 mg/kg). CONCLUSIONS: These results demonstrate that Ro 60-0175 is a useful probe of the importance of 5-HT2C activation in the control of food intake and support the hypothesis that activation of 5-HT2C receptors is a critical aspect of the hypophagic action of d-fenfluramine. The 5-HT2C receptor may prove to be a useful target in the development of clinically effective drugs for the treatment of obesity.

Aminopyridines↗
PubMed2000

Comparative effects of continuous infusion of mCPP, Ro 60-0175 and d-fenfluramine on food intake, water intake, body weight and locomotor activity in rats.

1. The aim of the study was to compare the effects of 14 day subcutaneous infusion of the 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP, 12 mg kg(-1) day(-1)) and Ro 60-0175 (36 mg kg(-1) day(-1)) and the 5-HT releasing agent and re-uptake inhibitor, d-fenfluramine (6 mg kg(-1) day(-1)), on food and water intake, body weight gain and locomotion in lean male Lister hooded rats. 2. Chronic infusion of all three drugs significantly reduced food intake and attenuated body weight gain. In contrast, drug infusion did not lead to significant reductions in locomotor activity in animals assessed 2 and 13 days after pump implantation. 3. In a subsequent 14 day study that was designed to identify possible tolerance during days 7 - 14, animals were given a subcutaneous infusion of mCPP (12 mg kg(-1) day(-1)) or d-fenfluramine (6 mg kg(-1) day(-1)) for either 7 or 14 days. During the first 7 days both drugs significantly reduced body weight gain compared to saline-infused controls; however, from day 7 onwards animals withdrawn from drug treatment exhibited an increase in body weight such that by day 14 they were significantly heavier than their 14-day drug-treated counterparts. 4. Both mCPP and d-fenfluramine reduced daily food intake throughout the infusion periods. For 14-day treated animals this hypophagia was marked during the initial week of the study but only minor during the second week. In light of the sustained drug effect on body weight, the data suggest that weight loss by 5-HT(2C) receptor stimulation may be only partly dependent on changes in food consumption and that 5-HT(2C) receptor agonists may have effects on thermogenesis. 5. These data suggest tolerance does not develop to the effects of d-fenfluramine, mCPP and Ro 60-0175 on rat body weight gain.

Analysis of Variance↗
PubMed2000

Measurement of anxiety in transgenic mice.

A wide range of approaches has been used to study anxiety in mice. All presuppose that aversive stimuli, such as foot shock or novelty, induce a central state of fear, which can be quantified through specific behavioural and physiological measures. This review discusses the validity of the various approaches in terms of their similarity to different human anxiety disorders, their ability to detect compounds which modulate human anxiety, and their relevance to animal defensive processes. The most commonly used models of anxiety suitable for screening transgenic and knockout mice are discussed, with an emphasis placed on controlling for factors which could confound results. As all models used to date have limitations and no single paradigm adequately models all aspects of anxiety, this review recommends the use of a broad range of anxiety models in order to provide a comprehensive characterisation of the behavioural phenotype of transgenic mice.

Animals↗
PubMed1999

Reduced satiating effect of d-fenfluramine in serotonin 5-HT(2C) receptor mutant mice.

RATIONALE: d-Fenfluramine stimulates the release of serotonin (5-HT) and is a potent inhibitor of the re-uptake of 5-HT into nerve terminals. Administration of d-fenfluramine suppresses food intake in both animals and humans. OBJECTIVE: We have investigated the role of the 5-HT2C receptor in mediating the effect of d-fenfluramine on mouse food intake and the behavioural satiety sequence. METHODS: Mutant mice lacking serotonin 5-HT2C receptors and wild-type animals were habituated to a daily presentation of wet mash. Animals were non-deprived and received d-fenfluramine (3-30 mg/kg) 30 min prior to being assessed for the presence of stereotypy and presented with wet mash. The behaviour of animals was observed for the subsequent 40 min and food intake was recorded. RESULTS: d-Fenfluramine dose-dependently inhibited the consumption of a palatable wet mash by the mice. d-Fenfluramine (3 mg/kg) significantly reduced the amount of wet mash consumed by wild-type mice and induced a temporal advance in the behavioural satiety sequence consistent with an enhancement of satiety. Mutant mice were less sensitive to the satiating effects of 3 mg/kg d-fenfluramine. Hence, this dose of d-fenfluramine had a reduced effect on both food consumption and the behavioural satiety sequence in the 5-HT2C mutant mice. In contrast, mutant mice showed an increased sensitivity to the stereotypy induced by high doses of d-fenfluramine (10, 30 mg/kg) compared to that of wild-type littermates. CONCLUSION: These data demonstrate a role for the 5-HT2C receptor in mediating d-fenfluramine-induced satiety.

Animals↗
PubMed1998

Utility of ethological analysis to overcome locomotor confounds in elevated maze models of anxiety.

The elevated plus-maze is a commonly used model to identify putative anxiolytic and anxiogenic drugs. However, the validity of elevated plus-maze and other recently developed variants such as the elevated zero-maze has recently been questioned on the grounds that both the reference anxiolytic drug chlordiazepoxide and the psychostimulant d-amphetamine increase open arm exploration and stimulate locomotor activity. These findings suggest that measures of "anxiety" in the elevated maze cannot be adequately dissociated from simple changes in locomotor activity, which may confound the interpretation of results obtained using these models. A variety of approaches to assess drug effects on locomotor activity in the elevated maze have been suggested, including the use of total and closed arm entries, as well as supplementary tests such as exploration of the holeboard apparatus. However, all these approaches utilise the measurement of exploration in a novel environment, and as such, could potentially be influenced by either changes in anxiety or locomotor activity. Recently, it has been shown that ethological measures of "risk assessment", such as stretched-attend postures and head-dipping, are sensitive indicators of drug-effects in the elevated maze. The present study assessed the utility of ethological analysis in dissociating locomotor activity from "anxiety" by comparing the effects of d-amphetamine to those of chlordiazepoxide in the rat elevated zero-maze. The results showed that both chlordiazepoxide and d-amphetamine increase the amount of time spent in the open arms and reduce "risk assessment" without increasing line crossing or rearing. These results confirm that under certain test conditions, psychostimulants are capable of producing "false-positives" in elevated maze models, and that both traditional methods and the ethological measures used in this study fail to unequivocally dissociate drug effects on anxiety from effects on locomotor activity. Further studies using other species and different classes of psychostimulants are warranted to determine the generality of these findings.

Animals↗
PubMed1997

Behavioural and pharmacological characterisation of the canopy stretched attend posture test as a model of anxiety in mice and rats.

The behavioural element, stretched attend posture (SAP), is an important component of the "risk-assessment" repertoire of defensive behaviour in rodents. The present experimental paradigm was devised as a novel and simple method of eliciting high levels of SAP in mice and rats. The SAP test apparatus comprised an elevated black Perspex circular platform. A smaller clear red Perspex circular "Canopy" was supported directly above the platform by a central pillar, thus dividing the platform into an inner, dimly lit covered zone and an outer, brightly lit exposed zone. In both the rat and mouse version of this model, vehicle-treated animals exhibited a marked preference for exploring the covered zone and also exhibited high baseline levels of SAP, particularly at the covered zone boundary whilst they investigated the exposed zone. In the mouse SAP test, the benzodiazepine receptor agonists, diazepam (0.5 mg/kg s.c.) and chlordiazepoxide (2 mg/kg s.c.), and the 5-HT1A receptor agonists, buspirone (1 and 3 mg/kg s.c.), ipsapirone (3 mg/kg s.c.) and 8-OH-DPAT (0.2 mg/kg s.c.), all significantly decreased the frequency of SAP without impairing motor activity. In the rat SAP test, diazepam (0.5 mg/kg s.c.) significantly decreased, whilst the anxiogenic 5-HT2C/1B receptor agonist, mCPP (0.25 and 0.5 mg/kg s.c.), significantly increased, the frequency of SAP. Ipsapirone (3 mg/kg s.c.) induced a non-specific behavioural inhibition. These data suggest that the "Canopy" SAP test is a useful paradigm to investigate risk assessment behaviour in both rats and mice, and may provide a sensitive novel rodent model of anxiety.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Blockade of pre- and post-synaptic 5-HT1A receptors does not modify the effect of fluoxetine or 5-hydroxytryptophan on ethanol and food intake in rats.

Selective serotonin reuptake inhibitors (SSRIs) or serotonin precursors inhibit ethanol and food intake by increasing the synaptic availability of 5-HT in the central nervous system. However, these agents can also increase 5-HT levels at somatodendritic 5-HT1A autoreceptors, with negative effects on serotonergic transmission. (+)WAY100135 [N-ter-butyl 3-4-(2-methoxy-phenyl) piperazin-1-yl-2-phenylpropanamide dihydrochloride] is a selective antagonist both at pre- and post-synaptic 5-HT1A receptors. The present study investigated the effect on ethanol and food intake of (+)WAY100135, given alone or coadministered with the SSRI fluoxetine or the 5-HT precursor 5-hydroxytryptophan (5-HTP) in genetically selected alcohol-preferring rats. Blockade of presynaptic 5-HT1A receptors after injection of (+)WAY100135, 0.1 or 1 microgram/rat, into the dorsal raphe did not significantly modify ethanol, food or total fluid intake. The same doses of (+)WAY100135 did not modify the inhibition of ethanol and food intake induced by intraperitoneal (i.p.) injection of fluoxetine, 5 mg/kg. Subcutaneous (s.c.) administration of (+)WAY100135 (1 or 10 mg/kg) did not affect the 3-h, or the overnight intake of ethanol, food or total fluids. Given together with i.p. fluoxetine (5 mg/kg) or s.c. 5-HTP (100 mg/kg plus carbidopa. 12.5 mg/kg), the same s.c. doses of (+)WAY100135 did not modify their inhibitory effect on ethanol and food consumption. Present findings suggest that blockade either of pre- or of pre- and postsynaptic 5-HT1A receptors does not potentiate the inhibitory effect of fluoxetine or 5-HTP on ethanol and food intake.

5-Hydroxytryptophan↗
PubMed1997

Devazepide attenuates dl-fenfluramine-induced suppression of gastric emptying but not food intake in the 17 h food-deprived rat.

Recently a number of studies have provided evidence which suggests that CCK and 5-HT interact in the control of food intake. The present experiments further examine this mechanism and the possibility that CCK and 5-HT interact in the control of gastric emptying. The selective CCK-A receptor antagonist, devazepide, (0.03-3.0 mg/kg) administered alone had no intrinsic effect on gastric emptying. Devazepide (0.1 and 0.3 mg/kg) blocked dl-fenfluramine-induced (3.0 mg/kg) suppression of gastric emptying. However, devazepide (0.03-3.0 mg/kg) failed to attenuate the anorectic effect of the same dose of dl-fenfluramine. These results suggest that under the present experimental conditions CCK and 5-HT interact in the regulation of gastric emptying but not food intake. Thus the interaction between CCK and 5-HT in the regulation of gastric emptying appears not to affect the control of ingestive behaviour.

Animals↗
PubMed1997

WAY100635 and latent inhibition in the rat: selective effects at preexposure.

The influence of the selective, silent 5HT1a antagonist WAY100635 (Wyeth Research Ltd) on the latent inhibition effect was examined in a within-subject, on-baseline conditioned suppression procedure in rats. WAY100635 was found to enhance the latent inhibition effect, producing a retardation in the acquisition of conditioned suppression following a level of stimulus preexposure known to be insufficient to produce a latent inhibition effect in control animals. This influence of the drug was restricted to its actions during the preexposure phase of the experiment, and the drug also abolished the unconditioned suppression of lever pressing that occurs on the first presentation of a novel auditory stimulus. These findings are discussed in terms of the possible influence of serotonergic manipulations on contextual processing, and also have important implications for current animal models of schizophrenia which stress the role of dopaminergic mechanisms in latent inhibition.

Acoustic Stimulation↗
PubMed1996

Effects of the selective angiotensin II receptor antagonists losartan and PD123177 in animal models of anxiety and memory.

There is increasing interest in the potential functional role of the octapeptide angiotensin II (AII) in psychiatric and cognitive disorders. The novel angiotensin II (AII) receptor antagonists, losartan and PD123177, selective for the AT1 and AT2 receptor subtypes respectively, constitute important pharmacological tools for the assessment of the behavioural consequences of modulation of AII function. The present series of studies investigated the effects of each compound in two animal models of anxiety, the rat elevated zero-maze and mouse light/dark box, and two models of working memory in the rat, the operant delayed matching to position (DMTP) task and the spatial reinforced alternation test in the T-maze. Our data indicate that both compounds (0.01-10 mg/kg s.c.) were without significant effect in any of the behavioural assays. Using the present methods and strains of laboratory rodents, these findings provide no support for the involvement of AII receptor function in the mediation of anxiety of working memory.

Angiotensin II↗
PubMed1996

Behavioural evidence that d-fenfluramine-induced anorexia in the rat is not mediated by the 5-HT1A receptor subtype.

These studies investigated the involvement of the 5-HT1A receptor in mediating d-fenfluramine-induced anorexia in the rat. Non-deprived, d-fenfluramine-treated (3.0 mg/kg) rats consumed a reduced amount of a palatable wet mash and showed a temporal advance in the behavioural sequence consistent with satiety. Thus, rats treated with d-fenfluramine ceased feeding and began resting before corresponding controls. Pretreatment with the selective 5-HT1A receptor antagonist WAY-100,635 (1.0 mg/kg) had no effect on either the reduced mash consumption or behavioural satiety sequence of d-fenfluramine-treated animals at a dose which was found to attenuate the anorexia induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg). Pretreatment with the non-selective 5-HT antagonist metergoline (1.0 mg/kg) attenuated the d-fenfluramine-induced reduction of mash consumption and the advanced offset of feeding. Metergoline pretreatment had no effect on the advanced onset of resting observed in d-fenfluramine-treated animals. These data suggest that d-fenfluramine reduces food intake, perhaps by enhancing satiety, via a mechanism which does not involve the 5-HT1A receptor subtype. The implications of these results to the utility of the behavioural satiety sequence as a measure of postprandial satiety are discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Effects of 5-HT1A receptor agonists, partial agonists and a silent antagonist on the performance of the conditioned emotional response test in the rat.

In the present study, the effects of 5-HT1A receptor ligands with varying degrees of intrinsic activity at the 5-HT1A receptor were examined in the conditioned emotional response (CER) test and their effects compared to those of the benzodiazepine receptor agonists, diazepam and chlordiazepoxide. Diazepam (3.0 mg/kg) and chlordiazepoxide (3.0 mg/kg), and the 5-HT1A receptor partial agonists, ipsapirone (10.0 mg/kg) and gepirone (3.0 mg/kg), alleviated conditioned suppression of lever pressing. The 5-HT1A receptor partial agonist, buspirone (0.1-1.0 mg/kg), the 5-HT1A receptor agonist, 8-OH-DPAT (0.01-0.10 mg/kg), and the 5-HT1A receptor antagonist, WAY-100635 (0.03-3.0 mg/kg), had no effects on conditioned fear. Neither enhancing the level of food deprivation nor pretreatment with the amnesic agent scopolamine induced anxiolytic-like effects in the present CER test. The anxiolytic-like effects of ipsapirone in this test were completely reversed by WAY-100635. These results indicate that 5-HT1A agonist, but not antagonist actions, induce an anxiolytic effect in the CER test in rats.

Analysis of Variance↗