- Email: [email protected]
P.4.d.002 The putative anxiolytic and antidepressant-like effect of Achillea millefolium L. extract in mice
S610
P.4.dAnxiety disorders and anxiolytics - Anxiolytics (basic)
subjective data were analyzed using SPSS version 16.0. Values of p < 0.05 were considered significant. Results: Independently of the treatment, fearful faces activated amygdala, insula, OFC and ACC bilaterally. Angry faces activated insula, OFC and ACC, but no haemodynamic responses were observed in amygdala. Diazepam attenuated the activation of right OFC to both emotions. The activations of bilateral insula to fearful faces and of left ACC to angry faces were attenuated by diazepam. In the behavioural task, diazepam impaired the recognition of fear in female faces, without effects on other emotions. Under the effects of diazepam, volunteers were less anxious at the end of the experimental session than under placebo. Conclusions: These data suggest that benzodiazepines can modulate brain activations to aversive stimuli differently, depending on the features of the stimuli. The attenuation of activation of insula to fearful faces, followed by impairment in the identification of fear in female faces and reduction in subjective anxiety, suggests a role of this brain structure in the anxiolytic effect of benzodiazepines. References [1] Ekman, P., Friesen, w.v. 1976. Pictures of facial affect. Palo Alto: Consulting Psychologists.
P.4.d Anxiety disorders and anxiolytics Anxiolytics (basic) IPA.d.0011 Spironolactone enhances extinction of contextual fear: a potential therapeutic for post-traumatic stress disorder? R. Andreatini1 *, E.M. Ninomiya1 , B.J. Martynhak1 , C. Da Cunha 1 . I Unioersidade Federal do Parana, Department of
Pharmacology, Curitiba, Brazil Objectives: There is evidence showing an association between Hypothalamus-Pituitary-Adrenal (BPA) axis and Post-Traumatic Stress Disorder - PTSD [1]. Since cortisol actions are mediated by mineralocorticoid (MR) and glucocorticoid (GR) receptors, the objective of the present study was to evaluate the effect MR (spironolactone) or GR (mifepristone) antagonists and GR agonist (dexamethasone) in the extinction of the contextual conditioned fear, an animal model of PTSD. Propranolol was used as positive control. Methods: Adult male Wistar rats (n=9-l0) were treated with spironolactone (10 mg/kg, sc), dexamethasone (lor 5 mg/kg ip), mifepristone (lOmg/kg, sc), and propranolol (lOmg/kg, sc, used as positive control) or their vehicle before the test sessions. In an additional experiment spironolactone (lOmg/kg, sc) was administered immediately after session 1 and session 2. In the training session of the contextual fear conditioning test [3] the rats were placed singly in the conditioning chamber for three minutes and received an electric foot shock (1.5 rnA, Is). After the shock the animals still remained in the box for one minute, after which they were returned to their homecages. During three consecutive days the animals were re-exposed to the conditioning chamber (9 min), without receiving the shock, and the freezing behavior was measured (test sessions). Data were analyzed by twoway ANOVA with treatment and sessions as factors. Differences between groups were evaluated by post hoc Student t test or oneway ANOVA followed by Newman-Keuls test. The accepted level of significance for the tests was p~0.05.
Results: The results showed that neither dexamethasone treatment nor mifepristone modified immobility time in test sessions compared to control (all P>0.05). On the other hand, spironolactone before each test session decreased immobility time (increase extinction) in sessions 2 and 3 when compared with the control (Table 1). Conversely, spironolactone administered after test sessions 1 and 2 did not alter immobility time relative to control (Table 1). Propranolol before each test sessions increased extinction in sessions 1 and 2 compared to the control (P < 0.05). Discussion: These results indicated that MR receptors playa role in conditioned fear extinction. Spironolactone exerts an effect only when administered before test session, which can indicate an impairment of memory retrieval, and not an enhancing of consolidation of new learning (association between context and shock absence), since post-session spironolactone did not affect the next session behavior. It was proposed that MR blockade may change the appraisal of aversive and frightening environment [2]. Thus, it is possible that blocking of MRs interfered with the interpretation of the context in which the conditioned contextual fear took place, thereby decreasing the freezing time throughout the experiment. Taken together, the present results indicated that MR receptor antagonists may be an option to PTSD treatment. Financial support: CNPq Table 1. Effect of spironolactone (lOmg/kg, s.c.) 60 min before or immediately after test sessions on freezing time (s) in contextual conditioned fear
Before test sessions Vehicle Spironolactone 10 After test sessions Vehicle Spironolactone 10
1st session
2nd session
3rd session
243 ±103 200±l07
192±8l 97±57*#
108±59# 57±44*#
196±93 l84±139
l4l±62 l70±163
87±49# l60±l85
Data represent mean + SEM, n=9-l0/group. #p <0.05 compared to 1st session with same treatment; *p < 0.05 compared to vehicle in the same test session. References [1] Bremner, J.D., Vythilingam, M., Vermetten, E., Afzal, N., Nazeer, A., Newcomer, J.w., Charney, D.S., 2004 Effects of dexamethasone on declarative memory function in posttraumatic stress disorder. Psychiatry Res 129, 1-10. [2] Oitzl, M.S. and De Kloet, E.R. (1992) Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behav. Neurosci. 106,62-71. [3] Pamplona, EA., Prediger, R.D.S., Pandolfo, P., Takahashi, R.N., 2006 The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory in rats. Psychopharmacology 188, 641--649.
1P.4.d.0021 The putative anxiolytic and antidepressantlike effect of Achillea millefolium L. extract in mice LP. Baretta1 , R.A. Felizardo 1 , y.F. Bimbato 1 , A. Gasparotto JUnior1, C. Kassuya'", R. Andreatini/ *. I Unioersidade
Paranaense, Department ofPharmacology, Umuarama, Brazil; 2 Unioersidade Federal do Parana, Department ofPharmacology, Curitiba, Brazil Objectives: In order to evaluate the potential of Achillea millefolium L. to treat anxiety and depression, we studied the effect
P.4.d Anxiety disorders and anxiolytics - Anxiolytics (basic) of acute and chronic effect of hydroethanolic extract of Achillea millefolium L. in mice submitted to the elevated plus-maze, forced swimming test and tail suspension test. Methods: Adult Swiss male mice were treated by gavage with hydroethanolic extract from aerial parts (leaves, stalks and stems) of Achillea millefolium L. (300mg/kg). Imipramine (IOmg/kg) and diazepam (0.75 mg/kg), both by gavage, were used as positive control. All drugs were administered at constant volume of 1 m1Ikg body weight. Picrotoxin (0.5 mg/kg) and flumazenil (1.0mg/kg) were used to evaluate the GABAI benzodiazepine participation in the Achillea millefolium L. anxiolytic-like effect. Data were analyzed by ANOVA followed by Newman-Keuls test. P < 0.05 was considered statistically significant. Results: Acute and chronic administration of Achillea millefolium L. increased the percentage of time spent in open arms without change in the closed arm entries, a similar profile of diazepam (ANOVA followed by Newman-Keuls test, p < 0.05). The anxiolytic-like effect of acute Achillea millefolium L. administration was not blocked by picrotoxin or flumazenil, which suggest that the anxiolytic-like effect ofthe extract is not mediated by GABAibenzodiazepine mechanism. In the forced swim test, chronic Achillea millefolium L. extract administration decreased the immobility time, an effect similar to antidepressant drugs [3], although imipramine was not effective in our experiment (probably due to low dose administered orally and small sample size). On the other hand, no effect was seen in the tail suspension test. Discussion: The preliminary results presented here indicated that hydroethanolic extract of Achillea millefolium L. has a potential antidepressant and anxiolytic effect. Although this latter result corroborate the anticonflict effect found by MolinaHemadez et al. [3], the antidepressant-like effect was observed for the first time. Moreover, the anxiolytic effect of Achillea millefolium L. appears to be independent from GABAibenzodiazepine neurotransmission, since it was not blocked by pre-treatment with flumazenil. It is interesting to note that it was showed that higher doses of Achillea millefolium L. than used in the present study did not induce clinical signs of toxicity after long-term treatment in rats [1]. Thus, Achillea millefolium L. has a potential to be used as anxiolytic and antidepressant drug. Financial support: CNPq Table I. The effect of chronic administration of hydroethanolic Achillea millefolium L. extract (300mg/kg), diazepam (0.75 mg/kg) and imipramine (10 mglkg) in elevated-plus maze, forced swim test, and tail suspension test (mean±SEM, n ~ 6)
Forced Swim - immobility (s) Tail Suspension test (s) Elevated Plus-Maze % open arms time % open arms entries Number closed arm entries
Vehicle
Achillea millefolium L.
Diazepam
Imipramine
23±!5 96±!4
5±3* 68±20
54±17 81±4
16±9 75±22
36±3 30±4 8±0.5
56±3* 59 ±4* 5±1
75±3* 60±7* 6±0.5
30±6 29±8 7±!
References [I] Dalsenter PRo Cavalcanti AM, Andrade AJ, Araujo SL, Marques MC. Reproductive evaluation of aqueous crude extract of Achillea millefolium L. (Asteraceae) in Wistar rats. Reprod Toxicol. 2004; 18(6):819-23. [2] Borsini F, Meli A. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology (Berl). 1988;94(2): 147-60. [3] Molina-Hernandez M, Tellez-Alcantara NP, Diaz MA, Perez Garcia J, Olivera Lopez Jl, Jaramillo MT. Anticonflict actions of aqueous extracts
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of flowers of Achillea millefolium L. vary according to the estrous cycle phases in Wistar rats. Phytother Res. 2004; 18(11):915-20.
1P.4.d.0031Increase in nociception and articular diameter after the dorsolateral periaqueductal gray chemical stimulation in rats L.J. Bertoglio 1 *, C.R. Tonussi 1 , E. Bressan1 , M.A. Martins 1 , C.A.J. Stem1 . 1Federal University ofSanta Catarina, Department ofPharmacology, Florianopolis SC, Brazil Purpose of study: It is recognized that anxiety is associated with an exacerbation of nociceptive symptoms in clinical situation [1]. Similarly, a transitory hypemociception is evoked in laboratory animals by non-noxious stressors such as mild restrain and vibration [2]. The dorsolateral periaqueductal gray (dlPAG) is a midbrain region modulating anxiety-related defensive behaviors such as inhibitory avoidance and risk assessment [3]. The aim of the present study was to test the hypothesis that the infusion of transient receptor potential vanilloid type 1 (TRPV1) channels agonist capsaicin, at putative anxiogenic-like doses, in the dlPAG would intensify nociceptive and inflammatory parameters displayed by rats in the knee-joint incapacitation test. Methods: One group of male Wistar rats was implanted with a guide cannula aimed at the dlPAG. One-week after surgery, each animal was infused into the dlPAG with vehicle (phosphate buffered saline containing 15 % of dimethyl sulfoxide) or capsaicin (0.1, 1.0 or 5.0 nmol in 0.2 uL), and 10 minutes later exposed for 5 minutes to the elevated-plus maze, an animal test of anxiety. Behavioral measures scored were the percentage of open arms time (%OAT) and open arms entries (%OAE), stretched attend postures (SAPs), and enclosed arm entries (EAE). To investigate the intra-dlPAG capsaicin effect on inflammatory nociception, another group of rats was evaluated during 6 h in the carrageenanlLPS-induced knee-joint incapacitation test. The behavioral measure scored was the paw elevation time (PET) during forced walk. The inflammatory parameters measured were the articular diameter and the number of leukocytes from synovial fluid. Results: ANOVA followed by Duncan's test (p < 0.05) showed a reduction in %OAT [vehicle (mean±S.E.M) = 18±4; capsaicin 1.0 nmol = 5±2] and in %OAE [vehicle (mean±S.E.M) = 37±6, capsaicin 1.0 nmol = 19±4] in rats exposed to the elevated plus-maze test after the infusion of capsaicin into the dlPAG. No significant changes were observed for SAPs and EAE. At the dose of 1.0 nmol, capsaicin also augmented the PET in the arthritic-induced incapacitation test on the second [vehicle (mean±S.E.M) = 22±7 s; capsaicin 1.0 nmol = 38±6 s] and on the third hour [vehicle (mean±S.E.M) = 14±2 s; capsaicin 1.0 nmol = 32±7 s] after the LPS injection. A similar effect was found in the articular diameter on the second hour [vehicle (mean±S.E.M) = 0.05±0.03mm; capsaicin 1.0 nmol = 0.11±0.01 mm]. No significant changes were observed for leukocyte number counting. Conclusions: The infusion of capsaicin (1.0 nmol) into the dlPAG increased inhibitory avoidance behavior, indicating an anxiogenic-like effect. This effect was accompanied by an increase in the nociceptive response and in the articular diameter. The present results confirm the hypothesis that a mild dlPAG chemical stimulation induced by the activation of TRPV1 channels may intensify nociceptive behavior and inflammatory edema. Financial support: CNPq, CAPES, FAPESP and FAPESC (Brazil).
P.4.dAnxiety disorders and anxiolytics - Anxiolytics (basic)
subjective data were analyzed using SPSS version 16.0. Values of p < 0.05 were considered significant. Results: Independently of the treatment, fearful faces activated amygdala, insula, OFC and ACC bilaterally. Angry faces activated insula, OFC and ACC, but no haemodynamic responses were observed in amygdala. Diazepam attenuated the activation of right OFC to both emotions. The activations of bilateral insula to fearful faces and of left ACC to angry faces were attenuated by diazepam. In the behavioural task, diazepam impaired the recognition of fear in female faces, without effects on other emotions. Under the effects of diazepam, volunteers were less anxious at the end of the experimental session than under placebo. Conclusions: These data suggest that benzodiazepines can modulate brain activations to aversive stimuli differently, depending on the features of the stimuli. The attenuation of activation of insula to fearful faces, followed by impairment in the identification of fear in female faces and reduction in subjective anxiety, suggests a role of this brain structure in the anxiolytic effect of benzodiazepines. References [1] Ekman, P., Friesen, w.v. 1976. Pictures of facial affect. Palo Alto: Consulting Psychologists.
P.4.d Anxiety disorders and anxiolytics Anxiolytics (basic) IPA.d.0011 Spironolactone enhances extinction of contextual fear: a potential therapeutic for post-traumatic stress disorder? R. Andreatini1 *, E.M. Ninomiya1 , B.J. Martynhak1 , C. Da Cunha 1 . I Unioersidade Federal do Parana, Department of
Pharmacology, Curitiba, Brazil Objectives: There is evidence showing an association between Hypothalamus-Pituitary-Adrenal (BPA) axis and Post-Traumatic Stress Disorder - PTSD [1]. Since cortisol actions are mediated by mineralocorticoid (MR) and glucocorticoid (GR) receptors, the objective of the present study was to evaluate the effect MR (spironolactone) or GR (mifepristone) antagonists and GR agonist (dexamethasone) in the extinction of the contextual conditioned fear, an animal model of PTSD. Propranolol was used as positive control. Methods: Adult male Wistar rats (n=9-l0) were treated with spironolactone (10 mg/kg, sc), dexamethasone (lor 5 mg/kg ip), mifepristone (lOmg/kg, sc), and propranolol (lOmg/kg, sc, used as positive control) or their vehicle before the test sessions. In an additional experiment spironolactone (lOmg/kg, sc) was administered immediately after session 1 and session 2. In the training session of the contextual fear conditioning test [3] the rats were placed singly in the conditioning chamber for three minutes and received an electric foot shock (1.5 rnA, Is). After the shock the animals still remained in the box for one minute, after which they were returned to their homecages. During three consecutive days the animals were re-exposed to the conditioning chamber (9 min), without receiving the shock, and the freezing behavior was measured (test sessions). Data were analyzed by twoway ANOVA with treatment and sessions as factors. Differences between groups were evaluated by post hoc Student t test or oneway ANOVA followed by Newman-Keuls test. The accepted level of significance for the tests was p~0.05.
Results: The results showed that neither dexamethasone treatment nor mifepristone modified immobility time in test sessions compared to control (all P>0.05). On the other hand, spironolactone before each test session decreased immobility time (increase extinction) in sessions 2 and 3 when compared with the control (Table 1). Conversely, spironolactone administered after test sessions 1 and 2 did not alter immobility time relative to control (Table 1). Propranolol before each test sessions increased extinction in sessions 1 and 2 compared to the control (P < 0.05). Discussion: These results indicated that MR receptors playa role in conditioned fear extinction. Spironolactone exerts an effect only when administered before test session, which can indicate an impairment of memory retrieval, and not an enhancing of consolidation of new learning (association between context and shock absence), since post-session spironolactone did not affect the next session behavior. It was proposed that MR blockade may change the appraisal of aversive and frightening environment [2]. Thus, it is possible that blocking of MRs interfered with the interpretation of the context in which the conditioned contextual fear took place, thereby decreasing the freezing time throughout the experiment. Taken together, the present results indicated that MR receptor antagonists may be an option to PTSD treatment. Financial support: CNPq Table 1. Effect of spironolactone (lOmg/kg, s.c.) 60 min before or immediately after test sessions on freezing time (s) in contextual conditioned fear
Before test sessions Vehicle Spironolactone 10 After test sessions Vehicle Spironolactone 10
1st session
2nd session
3rd session
243 ±103 200±l07
192±8l 97±57*#
108±59# 57±44*#
196±93 l84±139
l4l±62 l70±163
87±49# l60±l85
Data represent mean + SEM, n=9-l0/group. #p <0.05 compared to 1st session with same treatment; *p < 0.05 compared to vehicle in the same test session. References [1] Bremner, J.D., Vythilingam, M., Vermetten, E., Afzal, N., Nazeer, A., Newcomer, J.w., Charney, D.S., 2004 Effects of dexamethasone on declarative memory function in posttraumatic stress disorder. Psychiatry Res 129, 1-10. [2] Oitzl, M.S. and De Kloet, E.R. (1992) Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behav. Neurosci. 106,62-71. [3] Pamplona, EA., Prediger, R.D.S., Pandolfo, P., Takahashi, R.N., 2006 The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory in rats. Psychopharmacology 188, 641--649.
1P.4.d.0021 The putative anxiolytic and antidepressantlike effect of Achillea millefolium L. extract in mice LP. Baretta1 , R.A. Felizardo 1 , y.F. Bimbato 1 , A. Gasparotto JUnior1, C. Kassuya'", R. Andreatini/ *. I Unioersidade
Paranaense, Department ofPharmacology, Umuarama, Brazil; 2 Unioersidade Federal do Parana, Department ofPharmacology, Curitiba, Brazil Objectives: In order to evaluate the potential of Achillea millefolium L. to treat anxiety and depression, we studied the effect
P.4.d Anxiety disorders and anxiolytics - Anxiolytics (basic) of acute and chronic effect of hydroethanolic extract of Achillea millefolium L. in mice submitted to the elevated plus-maze, forced swimming test and tail suspension test. Methods: Adult Swiss male mice were treated by gavage with hydroethanolic extract from aerial parts (leaves, stalks and stems) of Achillea millefolium L. (300mg/kg). Imipramine (IOmg/kg) and diazepam (0.75 mg/kg), both by gavage, were used as positive control. All drugs were administered at constant volume of 1 m1Ikg body weight. Picrotoxin (0.5 mg/kg) and flumazenil (1.0mg/kg) were used to evaluate the GABAI benzodiazepine participation in the Achillea millefolium L. anxiolytic-like effect. Data were analyzed by ANOVA followed by Newman-Keuls test. P < 0.05 was considered statistically significant. Results: Acute and chronic administration of Achillea millefolium L. increased the percentage of time spent in open arms without change in the closed arm entries, a similar profile of diazepam (ANOVA followed by Newman-Keuls test, p < 0.05). The anxiolytic-like effect of acute Achillea millefolium L. administration was not blocked by picrotoxin or flumazenil, which suggest that the anxiolytic-like effect ofthe extract is not mediated by GABAibenzodiazepine mechanism. In the forced swim test, chronic Achillea millefolium L. extract administration decreased the immobility time, an effect similar to antidepressant drugs [3], although imipramine was not effective in our experiment (probably due to low dose administered orally and small sample size). On the other hand, no effect was seen in the tail suspension test. Discussion: The preliminary results presented here indicated that hydroethanolic extract of Achillea millefolium L. has a potential antidepressant and anxiolytic effect. Although this latter result corroborate the anticonflict effect found by MolinaHemadez et al. [3], the antidepressant-like effect was observed for the first time. Moreover, the anxiolytic effect of Achillea millefolium L. appears to be independent from GABAibenzodiazepine neurotransmission, since it was not blocked by pre-treatment with flumazenil. It is interesting to note that it was showed that higher doses of Achillea millefolium L. than used in the present study did not induce clinical signs of toxicity after long-term treatment in rats [1]. Thus, Achillea millefolium L. has a potential to be used as anxiolytic and antidepressant drug. Financial support: CNPq Table I. The effect of chronic administration of hydroethanolic Achillea millefolium L. extract (300mg/kg), diazepam (0.75 mg/kg) and imipramine (10 mglkg) in elevated-plus maze, forced swim test, and tail suspension test (mean±SEM, n ~ 6)
Forced Swim - immobility (s) Tail Suspension test (s) Elevated Plus-Maze % open arms time % open arms entries Number closed arm entries
Vehicle
Achillea millefolium L.
Diazepam
Imipramine
23±!5 96±!4
5±3* 68±20
54±17 81±4
16±9 75±22
36±3 30±4 8±0.5
56±3* 59 ±4* 5±1
75±3* 60±7* 6±0.5
30±6 29±8 7±!
References [I] Dalsenter PRo Cavalcanti AM, Andrade AJ, Araujo SL, Marques MC. Reproductive evaluation of aqueous crude extract of Achillea millefolium L. (Asteraceae) in Wistar rats. Reprod Toxicol. 2004; 18(6):819-23. [2] Borsini F, Meli A. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology (Berl). 1988;94(2): 147-60. [3] Molina-Hernandez M, Tellez-Alcantara NP, Diaz MA, Perez Garcia J, Olivera Lopez Jl, Jaramillo MT. Anticonflict actions of aqueous extracts
S611
of flowers of Achillea millefolium L. vary according to the estrous cycle phases in Wistar rats. Phytother Res. 2004; 18(11):915-20.
1P.4.d.0031Increase in nociception and articular diameter after the dorsolateral periaqueductal gray chemical stimulation in rats L.J. Bertoglio 1 *, C.R. Tonussi 1 , E. Bressan1 , M.A. Martins 1 , C.A.J. Stem1 . 1Federal University ofSanta Catarina, Department ofPharmacology, Florianopolis SC, Brazil Purpose of study: It is recognized that anxiety is associated with an exacerbation of nociceptive symptoms in clinical situation [1]. Similarly, a transitory hypemociception is evoked in laboratory animals by non-noxious stressors such as mild restrain and vibration [2]. The dorsolateral periaqueductal gray (dlPAG) is a midbrain region modulating anxiety-related defensive behaviors such as inhibitory avoidance and risk assessment [3]. The aim of the present study was to test the hypothesis that the infusion of transient receptor potential vanilloid type 1 (TRPV1) channels agonist capsaicin, at putative anxiogenic-like doses, in the dlPAG would intensify nociceptive and inflammatory parameters displayed by rats in the knee-joint incapacitation test. Methods: One group of male Wistar rats was implanted with a guide cannula aimed at the dlPAG. One-week after surgery, each animal was infused into the dlPAG with vehicle (phosphate buffered saline containing 15 % of dimethyl sulfoxide) or capsaicin (0.1, 1.0 or 5.0 nmol in 0.2 uL), and 10 minutes later exposed for 5 minutes to the elevated-plus maze, an animal test of anxiety. Behavioral measures scored were the percentage of open arms time (%OAT) and open arms entries (%OAE), stretched attend postures (SAPs), and enclosed arm entries (EAE). To investigate the intra-dlPAG capsaicin effect on inflammatory nociception, another group of rats was evaluated during 6 h in the carrageenanlLPS-induced knee-joint incapacitation test. The behavioral measure scored was the paw elevation time (PET) during forced walk. The inflammatory parameters measured were the articular diameter and the number of leukocytes from synovial fluid. Results: ANOVA followed by Duncan's test (p < 0.05) showed a reduction in %OAT [vehicle (mean±S.E.M) = 18±4; capsaicin 1.0 nmol = 5±2] and in %OAE [vehicle (mean±S.E.M) = 37±6, capsaicin 1.0 nmol = 19±4] in rats exposed to the elevated plus-maze test after the infusion of capsaicin into the dlPAG. No significant changes were observed for SAPs and EAE. At the dose of 1.0 nmol, capsaicin also augmented the PET in the arthritic-induced incapacitation test on the second [vehicle (mean±S.E.M) = 22±7 s; capsaicin 1.0 nmol = 38±6 s] and on the third hour [vehicle (mean±S.E.M) = 14±2 s; capsaicin 1.0 nmol = 32±7 s] after the LPS injection. A similar effect was found in the articular diameter on the second hour [vehicle (mean±S.E.M) = 0.05±0.03mm; capsaicin 1.0 nmol = 0.11±0.01 mm]. No significant changes were observed for leukocyte number counting. Conclusions: The infusion of capsaicin (1.0 nmol) into the dlPAG increased inhibitory avoidance behavior, indicating an anxiogenic-like effect. This effect was accompanied by an increase in the nociceptive response and in the articular diameter. The present results confirm the hypothesis that a mild dlPAG chemical stimulation induced by the activation of TRPV1 channels may intensify nociceptive behavior and inflammatory edema. Financial support: CNPq, CAPES, FAPESP and FAPESC (Brazil).