title: Stress-induced vocalisation in adult animals. A valid model of anxiety?
abstract: The post-stimuli anticipatory vocalisations that follow stressful and painful conditions are suggested as a quantitative measure of the emotional state of fear and anxiety in animal models. Adult rats emit characteristic 22-kHz ultrasound vocalisations consisting of 20-30 kHz calls with a mean duration of 300-600 ms as response to aversive stimuli (e.g. inescapable electric footshock, acoustic or air-puff stimuli, agonistic encounter or withdrawal from treatment with drugs of abuse). The vocalisations are accompanied by defensive submissive behaviour and signal a refractory, socially withdrawn or helpless state. Furthermore, brain structures that are involved in the mediation of anxiety-like behaviour, e.g. the dorsal periaqueductal grey and cortical areas, are also important for modulation of ultrasonic vocalisation. Benzodiazepines, e.g. diazepam, inhibit shock-induced ultrasonic vocalisation although the active doses are generally close to those that produce sedation and muscle relaxation. Selective serotonin reuptake inhibitors and other antidepressants that preferentially enhance serotonergic neurotransmission inhibit footshock-induced ultrasonic vocalisation. The 5-HT(2) receptor antagonistic properties of fluoxetine may explain why only partial inhibition is achieved. The biphasic dose-response curve of the racemic drug, citalopram, may perhaps be ascribed to an attenuating effect of R-citalopram. Tricyclic antidepressants, e.g. imipramine, and antidepressants that preferentially enhance catecholaminergic neurotransmission, e.g. reboxetine and venlafaxine, are inactive. Classical antipsychotics like haloperidol have no or a weak inhibitory effect. Serotonin plays a major role in the mediation of ultrasonic vocalisation, and in particular 5-HT(1A) and 5-HT(2) receptors are found to have a prominent role. Different serotonergic pathways are likely to be involved in the mediation of the anxiolytic-like response, e.g. the pathway ascending from the dorsal raphe nucleus through the medial forebrain bundle to the amygdala and frontal cortex mediating conditioned/learned anxiety and another pathway ascending from the dorsal raphe nucleus to the periaqueductal grey mediating unconditioned/fight flight anxiety. Dopamine D(2) receptor agonists are potent inhibitors of footshock-induced ultrasonic vocalisation. The role of dopamine D(1) receptors and adrenoceptors remains to be further elucidated. Several other neurotransmitters are involved in the mediation of ultrasonic vocalisation, e.g. acetylcholine, histamine and glutamate. There is also a need for further studies of how changes in stress-axis function may modulate ultrasonic vocalisation and for studies of the effects of chronic drug treatment on ultrasonic vocalisation.
authors.affiliation: Neuropharmacology Research, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Copenhagen-Valby, Denmark. cs@lundbeck.com
authors.forename: Connie
authors.initials: C
authors.lastname: Sánchez
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology*; D001921:Brain / Q000503:physiopathology; D004195:Disease Models, Animal; D018377:Neurotransmitter Agents / Q000378:metabolism; D013315:Stress, Psychological / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D018377:Neurotransmitter Agents