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  • 1
    ISSN: 1432-2072
    Schlagwort(e): Ultrasonic distress vocalizations ; Adult rat ; Anxiety ; Panic disorder ; Situational panic attack ; Alprazolam ; 5-HT uptake inhibitor ; Fluvoxamine ; Clomipramine ; Imipramine ; Diazepam ; Chlordiazepoxide ; Benzodiazepine ; 5-HT1A receptor agonist ; NA uptake inhibitor ; Dopamine-D2 receptor antagonist
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats may produce ultrasonic vocalizations (USV) in threatening situations. USV of adult male rats in association with aversive stimulation was evaluated as a screening method for anxiolytic drugs. The triazolobenzodiazepine alprazolam, the 5-HT uptake inhibitors fluvoxamine and clomipramine, the mixed 5-HT/NA uptake inhibitor imipramine, the full 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan, the partial 5-HT1A receptor agonists buspirone, ipsapirone and BMY 7378, theα 2-adrenoceptor agonist clonidine and theα 2-adrenoceptor antagonist yohimbine reduced conditioned USV. The classical benzodiazepines (BZD) diazepam and chlordiazepoxide were ineffective or had a very low potency to decrease USV. The partial BZD receptor agonists bretazenil, alpidem and zolpidem, the BZD receptor antagonist flumazenil, the NA uptake inhibitors desipramine and maprotiline, and the 5-HT3 receptor antagonist ondansetron had no effect on conditioned USV. The dopamine-D2 receptor antagonist haloperidol reduced USV at a very high dose. In separate experiments the effects of these drugs on locomotor activity were assessed. There was, however, no direct relationship between effects on motor behaviour and USV. In conclusion, the sensitivity of conditioned USV to 5-HT uptake inhibitors and alprazolam versus the insensitivity to classical benzodiazepines and NA uptake inhibitors provides a very interesting profile, which closely resembles the psychopharmacology of panic disorder. Also the face validity of conditioned USV towards situational panic attacks is high. We therefore propose conditioned USV in adult male rats as a novel behavioural paradigm to screen for anti-panic drugs.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-2072
    Schlagwort(e): Anxiety ; Fear-potentiated startle ; Behavioral models ; Predictive validity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The fear-potentiated startle (PSR) paradigm is a putative behavioral model for the determination of anxiolytic properties of drugs. The present study further investigated the predictive validity of the model. Predictive validity is high, when only drugs clinically used as anxiolytics attenuate PSR dose dependently. Results showed that startle potentiation decreased dose dependently after the administration of the anxiolytics CDP (2.5–10 mg/kg, IP) and alprazolam (1–3 mg/kg, IP). After administration of the clinically non-anxiolytic drugs amitriptyline (2.5–10 mg/kg, IP), carbamazepine (5–20 mg/kg, IP), fentanyl (0.0025–0.04 mg/kg, SC), naloxone (2.5–10 mg/kg, IP), nicotine (0.4–1.6 mg/kg, IP), alcohol (500–2000 mg/kg, IP), andd-amphetamine (0.6–2.4 mg/kg, IP), a dose-dependent decrease in startle potentiation was not found. The PSR correctly discriminated most of the drugs tested in clinically anxiolytic and clinically non-anxiolytic drugs. However, haloperidol behaved as a false positive, and results of nicotine and alcohol were at variance with results reported by others.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-2072
    Schlagwort(e): Key words Prefrontal cortex ; Dopamine ; Anxiety ; Drug discrimination ; Pentylenetetrazol ; Chlordiazepoxide ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: The prefrontal cortical (PFC) dopamine (DA) system has been implicated in anxiety-related behavioral changes, but direct, unequivocal support for this idea is sparse. Objectives: The present aim was to study the functional significance of prefrontal DA using the pentylenetetrazol (PTZ) discrimination model of anxiety. A comparison was made with its role in the cue of the anxiolytic drug chlordiazepoxide (CDP). Methods: Two groups of rats were trained to discriminate either PTZ (20 mg/kg, s.c.) or CDP (10 mg/kg, i.p.) from saline using an operant drug discrimination procedure. After prolonged training, half of each group was used to assess biochemical changes induced by both drugs in different sub areas of the PFC. For the remaining rats, discrimination training continued and generalization tests with PTZ and CDP were performed. Rats were then provided with bilateral guide cannulae aimed at the ventromedial (vm) PFC, and the effects of local infusions of DAergic drugs on discriminative performance were evaluated. Results: CDP did not affect PFC DA activity, but PTZ increased the DOPAC/DA ratio in the vmPFC selectively. Generalization tests showed that the cues of PTZ and CDP were dose dependent. In PTZ-trained rats, infusions of the DA receptor antagonist cis-flupenthixol into the vmPFC blocked the PTZ cue dose dependently, whereas the agonist apomorphine partially generalized to this cue. In CDP-trained rats, neither drug antagonized or generalized to the CDP cue, showing that PFC DA is not critically involved in the CDP cue and that local pharmacological manipulations of PFC DA do not affect discriminative abilities per se. Conclusions: The DAergic innervation of the PFC is directly involved in the behavioral effects of PTZ, suggesting a role for it in anxiety.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 121 (1995), S. 81-90 
    ISSN: 1432-2072
    Schlagwort(e): Stretched approach posture ; Ambivalent behaviour ; Intention movements ; Ethological observation ; Rat ; Anxiety disorders ; Benzodiazepines ; 5-HT1A receptor agonists ; 5-HT uptake inhibitors ; Clonidine ; Clorgyline ; Anxiogenic drugs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of various psychotropic drugs on the ambivalent behaviour “stretched approach posture” (SAP) in the rat was assessed. SAP was elicited after a mild startle reaction due to physical contact with an electrified prod at one end of a straight runway. Using ethological observation methods, SAP as well as intention movements, prod contact, crossings, rearing, exploration, grooming and immobility were recorded. The benzodiazepine receptor agonists chlordiazepoxide, diazepam and alprazolam, the 5-HT1A receptor agonists flesinoxan and ipsapirone and the 5-HT uptake inhibitor clomipramine selectively (no effect on crossings) reduced SAP. Except for alprazolam, these drugs also reduced intention movements. In addition, chlordiazepoxide and diazepam enhanced prod contact. Reductions of SAP and intentions with concomitant reductions of crossings (nonspecific anti-ambivalent effects) were established for the α2-adrenoceptor agonist clonidine and the MAO inhibitor clorgyline. The 5-HT uptake inhibitor fluvoxamine suppressed intention movements, but not SAP. The mixed 5-HT/NA uptake inhibitor imipramine did not significantly affect SAP or intentions, but reduced crossings. The 5-HT2C/1B receptor agonist m-CPP, the inverse BZD receptor agonists FG 7142 and DMCM, and the α2-adrenoceptor antagonist yohimbine, to all of which putative anxiogenic effects have been ascribed, had no effect on SAP directed towards the prod. m-CPP, however, produced an increase in the stretched posture directed away from the prod (SAwayP). FG 7142 reduced intentions while strongly enhancing immobility (freezing). SAwayP and/or freezing may possibly reflect anxiogenic properties of drugs. The putative anxiogenic drug pentylenetetrazol false positively reduced SAP while increasing exploration. The dopamine-D2 receptor antagonist haloperidol and the catecholamine releaserdl-amphetamine had no effect on ambivalent behaviour. The muscarine receptor antagonist scopolamine reduced SAP and intentions while stimulating crossings. Finally, the 5-HT2C receptor antagonist ritanserine, the CCKA receptor antagonist devazepide, the CCKB receptor antagonist L-365.260 and the strychnine-insensitive glycine site antagonist 7-Cl-kynurenic acid were without effect on the behaviours in this paradigm using single doses. In conclusion, SAP and intention movements were reduced selectively by anxiolytic agents from different classes, including benzodiazepine receptor agonists, 5-HT1A receptor agonists and a 5-HT uptake inhibitor, whereas an α2-adrenoceptor agonist and a MAO inhibitor reduced SAP non-selectively. SAP in relation to other behaviours may therefore serve as a valuable paradigm to characterize anxiolytic drugs.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 126 (1996), S. 104-109 
    ISSN: 1432-2072
    Schlagwort(e): Anxiety ; Fear-potentiated startle response ; Predictive validity ; Reliability ; Oxazepam ; Flesinoxan ; Fluvoxamine ; Strychnine-potentiated startle response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The fear-potentiated startle response paradigm is used to investigate anxiolytic properties of drugs. The first objective of the present study was to further investigate the predictive validity of this paradigm. The anxiolytics chlordiazepoxide (2.5–10 mg/kg IP) and oxazepam (1–10 mg/kg PO) and the putative anxiolytic flesinoxan (1–10 mg/kg PO) decreased startle potentiation dose-dependently, indicating an anxiolytic effect. The antidepressant fluvoxamine (5–20 mg/kg PO) did not affect startle potentiation. Ideally, anxiolytic drugs attenuate startle potentiation without affecting control startle levels, although some studies report altered control startle amplitudes. The second objective was to investigate whether different effects on control startle amplitudes are related to different startle devices. Therefore, the drugs were tested in two laboratories. Results showed no significant differences between laboratories, indicating that equipment is not a critical factor in the drug-induced alteration of control startle levels. In an additional experiment, it was shown that flesinoxan (10 mg/kg PO) did not affect strychnine-induced startle potentiation, supporting the idea that the attenuating effect of flesinoxan on the fear-potentiated startle response is due to its anxiolytic properties. Thus, the fear-potentiated startle response paradigm appears a valid and reliable model for anxiolytic properties of drugs.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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