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P.4.b.008 Effects of midazolam, propranolol or scopolamine treatment in rats submitted to an olfactory fear conditioning paradigm
P.4.b Anxiety disorders and anxiolytics – Anxiety disorders (basic) P.4.b.008 Effects of midazolam, propranolol or scopolamine treatment in rats submitted to an olfactory fear conditioning paradigm J.A.V. Kroon1 ° , A.P. Carobrez1 . 1 Universidade Federal de Santa Catarina, Farmacologia/CCB, Florian´opolis, Brazil Purpose: Fear conditioning occurs when an emotionally neutral stimulus acquires threatening characteristics (CS) after being paired with an aversive unconditioned stimulus (US). Olfactory stimuli that were associated with aversive emotional experiences have been considered to be precipitants of trauma symptoms in the posttraumatic stress disorder [1]. In rodents, conditioned responses are more pronounced toward olfactory stimulus [2] and the usefulness of olfactory cues, as CS, was applied to evaluate the influence of midazolam (MDZ), propranolol (PRO) and scopolamine (SCO) on acquisition, consolidation and expression of a conditioning emotional response (CER). Methods and Results: The experimental paradigm comprised two phases: the acquisition (US+CS pairing) and the expression of CER. The sessions were spaced 24 hours each other within 5 subsequent days. The acquisition phase consisted of two sessions, in a chamber connected to a shock generator. Male Wistar rats were placed in the conditioning chamber and allowed to explore freely on day 1. On day 2, subjects received five pairings of footshock (40 s inter-trial period; 0.4 mA/2s) and coffee odor (CS). The expression of CER was detected in an odor box comprising an open and an enclosed communicating compartment. This phase consisted of three sessions: familiarization (neutral odor), test (CS exposure) and context (neutral odor). The following CER were measured: the %time spent near the odor source (%approach time; %AT) and %time in the enclosed compartment (%hide time; %HT). Table shows the mean %AT and %HT following MDZ (0.5 mg/kg), PRO (10 mg/kg) and SCO (0.6 mg/kg) treatment. Statistical analysis revealed that the MDZ injection 30 min prior the conditioning session (PreCond; day 2) and immediately after the conditioning session (PostCond), significantly increased %AT and reduced %HT, when compared to the saline group. Statistical analysis also revealed that subjects treated with PRO both PreCond and 30 min prior to the test session (PreTest; day 4) showed an increase in %AT and when PRO was injected PostCond, a reduction in %HT was detected. Finally, SCO treatment PreCond produced a significant reduction in %HT and when injected PreTest produced an increase in %AT and a reduction in %HT. Treatment % Approach Time
Saline MDZ PRO SCO
% Hide Time
PreCond
PostCond
PreTest
PreCond
PostCond
PreTest
10.8±1.4# 22.0±2.9* 19.3±4.1* 21.4±7.3
9.9±2.0# 25.7±6.3* 16.9±5.1 19.2±6.4
10.8±2.3# 12.9±2.6 23.4±6.6* 26.1±6.9*
74.9±3.4# 51.1±6.2* 60.3±7.2 55.4±6.6*
77.8±3.3# 49.8±8.6* 56.7±10.2* 66.0±7.0
70.8±4.4# 69.8±7.8 57.4±8.3 49.8±8.9*
Baseline levels, neutral odor: %AT = 26.8±1.5; %HT = 39.0±1.9. *p < 0.05 vs saline group; # p < 0.05 vs baseline levels – ANOVA followed by Duncan.
Conclusions: 1) MDZ was able to interfere with the CS-US association and with the retention of the aversive information; 2) The behavioral responses observed after PRO treatment suggest that in addition to the interference with the CS-US pairing and with the retention of the aversive information, when applied PreTest, PRO was able to acutely reduce CER; and 3) Although the treatment with SCO failed to interfere with the retention of the acquired information, it impaired the CS-US association when
S491
injected PreCond and also was able to acutely reduce CER when applied PreTest. The results suggest the usefulness of the olfactory fear conditioning paradigm to test drugs effects on the acquisition, the consolidation and the expression of CER. Financial Support: CAPES, CNPq, FAPESP, FAPESC, UFSC References [1] Vermetten, E., Schmahl, C., Southwick, S.M., Bremner, J.D., 2007, Positron tomographic emission study of olfactory induced emotional recall in veterans with and without combat-related posttraumatic stress disorder. Psychopharmacol Bull 40, 8−30. [2] Otto, T., Cousens, G., Herzog, C., 2000, Behavioral and neuropsychological foundations of olfactory fear conditioning. Behav Brain Res 110, 119−28.
P.4.b.009 Relationship of panic and agoraphobia: rethinking of a diagnostic concept? A. Nocon1 ° , H.U. Wittchen2 , K. Beesdo2 , D.S. Pine3 , 1 Max-PlanckM. H¨ofler2 , R. Lieb4 , A.T. Gloster5 . Institute of Psychiatry, Molecular Psychology, Munich, Germany; 2 Technische Universit¨ at Dresden, Institute of Clinical Psychology and Psychotherapy, Dresden, Germany; 3 National Institute of Mental Health Division of Intramural Research Programs, Mood and Anxiety Disorders Program, Bethesda MD, USA; 4 University of Basel, Epidemiology and Health Psychology, Basel, Switzerland; 5 Universit¨at Dresden, Institute of Clinical Psychology and Psychotherapy, Dresden, Germany Background: The diagnostic status of panic disorder (PD) and agoraphobia (AG) continues to be a matter of debate in psychopathology research. DSM-IVs criteria are based on the symptom progression model that agoraphobia is a conditioned response to a sudden onset of unexplained panic attacks (PA), and that it is the recurrence of panic attacks the agoraphobic patient is afraid of. Alternative views contend that the mere presence of panic predicts less about the nature of the clinical syndrome than the type of situation that cues the panic because panic attacks are an unspecific phenomenon which can be found in many other conditions and a rather unspecific diagnostic predictor; this view also sees agoraphobia as a diagnostic category in its own right, independent of panic attacks or panic-like features. Aims: 1. To prospectively investigate the natural development of panic and agoraphobia in the community without taking into account DSM-IVs hierarchical rules 2. to describe the patterns of incidence of panic attacks, agoraphobia, and panic disorder, 3. to examine their natural course and reciprocal transitions with each other and 4. to examine the degree to which they differ with regard to selected clinical correlates. Methods: A representative community sample of N = 3021 adolescents and young adults aged 14−24 years at baseline was followed up over a period of 10 years in up to 4 waves. DSM-IV symptoms and syndromes were assessed face-to-face via standardized interview (M-CIDI) with and without using the DSM-IV hierarchy rules for panic and agoraphobia. Results: Lifetime incidences were 9.4% for PA, 3.4% for panic disorder (PD) (with AG: 1.9%, without AG: 1.5%) and 5.3% for AG (with PA: 2.5%, without PA: 2.8%). Incidence patterns for PA, PD and AG revealed differences in age of onset, incidence risk and gender differentiation. Temporally primary PA and PD was
Saline MDZ PRO SCO
% Hide Time
PreCond
PostCond
PreTest
PreCond
PostCond
PreTest
10.8±1.4# 22.0±2.9* 19.3±4.1* 21.4±7.3
9.9±2.0# 25.7±6.3* 16.9±5.1 19.2±6.4
10.8±2.3# 12.9±2.6 23.4±6.6* 26.1±6.9*
74.9±3.4# 51.1±6.2* 60.3±7.2 55.4±6.6*
77.8±3.3# 49.8±8.6* 56.7±10.2* 66.0±7.0
70.8±4.4# 69.8±7.8 57.4±8.3 49.8±8.9*
Baseline levels, neutral odor: %AT = 26.8±1.5; %HT = 39.0±1.9. *p < 0.05 vs saline group; # p < 0.05 vs baseline levels – ANOVA followed by Duncan.
Conclusions: 1) MDZ was able to interfere with the CS-US association and with the retention of the aversive information; 2) The behavioral responses observed after PRO treatment suggest that in addition to the interference with the CS-US pairing and with the retention of the aversive information, when applied PreTest, PRO was able to acutely reduce CER; and 3) Although the treatment with SCO failed to interfere with the retention of the acquired information, it impaired the CS-US association when
S491
injected PreCond and also was able to acutely reduce CER when applied PreTest. The results suggest the usefulness of the olfactory fear conditioning paradigm to test drugs effects on the acquisition, the consolidation and the expression of CER. Financial Support: CAPES, CNPq, FAPESP, FAPESC, UFSC References [1] Vermetten, E., Schmahl, C., Southwick, S.M., Bremner, J.D., 2007, Positron tomographic emission study of olfactory induced emotional recall in veterans with and without combat-related posttraumatic stress disorder. Psychopharmacol Bull 40, 8−30. [2] Otto, T., Cousens, G., Herzog, C., 2000, Behavioral and neuropsychological foundations of olfactory fear conditioning. Behav Brain Res 110, 119−28.
P.4.b.009 Relationship of panic and agoraphobia: rethinking of a diagnostic concept? A. Nocon1 ° , H.U. Wittchen2 , K. Beesdo2 , D.S. Pine3 , 1 Max-PlanckM. H¨ofler2 , R. Lieb4 , A.T. Gloster5 . Institute of Psychiatry, Molecular Psychology, Munich, Germany; 2 Technische Universit¨ at Dresden, Institute of Clinical Psychology and Psychotherapy, Dresden, Germany; 3 National Institute of Mental Health Division of Intramural Research Programs, Mood and Anxiety Disorders Program, Bethesda MD, USA; 4 University of Basel, Epidemiology and Health Psychology, Basel, Switzerland; 5 Universit¨at Dresden, Institute of Clinical Psychology and Psychotherapy, Dresden, Germany Background: The diagnostic status of panic disorder (PD) and agoraphobia (AG) continues to be a matter of debate in psychopathology research. DSM-IVs criteria are based on the symptom progression model that agoraphobia is a conditioned response to a sudden onset of unexplained panic attacks (PA), and that it is the recurrence of panic attacks the agoraphobic patient is afraid of. Alternative views contend that the mere presence of panic predicts less about the nature of the clinical syndrome than the type of situation that cues the panic because panic attacks are an unspecific phenomenon which can be found in many other conditions and a rather unspecific diagnostic predictor; this view also sees agoraphobia as a diagnostic category in its own right, independent of panic attacks or panic-like features. Aims: 1. To prospectively investigate the natural development of panic and agoraphobia in the community without taking into account DSM-IVs hierarchical rules 2. to describe the patterns of incidence of panic attacks, agoraphobia, and panic disorder, 3. to examine their natural course and reciprocal transitions with each other and 4. to examine the degree to which they differ with regard to selected clinical correlates. Methods: A representative community sample of N = 3021 adolescents and young adults aged 14−24 years at baseline was followed up over a period of 10 years in up to 4 waves. DSM-IV symptoms and syndromes were assessed face-to-face via standardized interview (M-CIDI) with and without using the DSM-IV hierarchy rules for panic and agoraphobia. Results: Lifetime incidences were 9.4% for PA, 3.4% for panic disorder (PD) (with AG: 1.9%, without AG: 1.5%) and 5.3% for AG (with PA: 2.5%, without PA: 2.8%). Incidence patterns for PA, PD and AG revealed differences in age of onset, incidence risk and gender differentiation. Temporally primary PA and PD was