Central α- and β-thujone: similar anxiogenic-like effects and differential modulation on GABAA receptors in neonatal chicks.
The convulsant effects of α-thujone are attributed to inhibitory actions on the GABAA receptor. We investigated, for the first time, the effects of α-thujone or β-thujone administrated centrally on the fear/anxiety behaviour of 3-day-old chicks in an Open Field and their modulation on the GABAA receptor. Higher doses were convulsant by eliciting a toxic and excitatory action, with the results showing that a dose of 78 nmol of either of the two diastereoisomers had an anxiogenic-like effect observed as an increased latency to ambulate and a reduced locomotor activity in an Open Field. Nevertheless, only the central administration of α-thujone reversed the increase induced by acute stress in the flunitrazepam-sensitive GABAA receptor recruitment. These findings demonstrated that α-thujone, when intracerebroventricularly administered, suppressed the GABAA receptor recruitment induced by acute stress, maybe due to α-thujone blocking the benzodiazepine binding site or another site of the GABAA complex. However, it should not be discarded that acute stress associated with novelty may have induced the recruitment of a subpopulation of GABAA receptors more sensitive to α-thujone than to the constitutive receptors, or that this monoterpene could have inhibited any protein or enzyme trafficking that modulated the phosphorylation of the receptor involved in the turnover of GABAA receptor. β-Thujone showed behavioural effects similar to its diastereoisomer α-thujone. However, its action mechanism may have been mediated by other neurotransmitter systems, such as the serotonergic one or by a different biological effectiveness due to a distinct stereochemistry at the specific site of the GABAA receptor.
Instituto de Investigaciones Biológicas y Tecnológicas (IIByT-CONICET), Departamento de Química, Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Córdoba, Cordoba 5000, Argentina.
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Rivera
Instituto de Investigaciones Biológicas y Tecnológicas (IIByT-CONICET), Departamento de Química, Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Córdoba, Cordoba 5000, Argentina.
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Instituto Multidisciplinario de Biología Vegetal (IMBIV-CONICET), Departamento de Química, Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, 5016 Córdoba, Argentina.
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Zunino
Instituto de Investigaciones Biológicas y Tecnológicas (IIByT-CONICET), Departamento de Química, Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Córdoba, Cordoba 5000, Argentina.
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Baiardi
Instituto de Investigaciones Biológicas y Tecnológicas (IIByT-CONICET), Departamento de Química, Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Córdoba, Cordoba 5000, Argentina. Electronic address: nsalvatierra@efn.uncor.edu.
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Salvatierra
D000818:Animals; D000831:Animals, Newborn; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced*; D000081008:Bicyclic Monoterpenes; D002645:Chickens; D005239:Fear / Q000187:drug effects*; D005260:Female; D005445:Flunitrazepam / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D057967:Infusions, Intraventricular; D008297:Male; D039821:Monoterpenes / Q000008:administration & dosage / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D014151:Anti-Anxiety Agents; D000081008:Bicyclic Monoterpenes; D018757:GABA Modulators; D039821:Monoterpenes; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C005790:beta-thujone
GABA(A) receptor recruitment; anxiety; α-thujone; β-thujone