科研之友
微信
新浪微博
Facebook
分享链接
摘要
The convulsant effects of a-thujone are attributed to inhibitory actions on the GABA(A) receptor. We investigated, for the first time, the effects of a-thujone or p-thujone administrated centrally on the fear/anxiety behaviour of 3-day-old chicks in an Open Field and their modulation on the GABA(A) 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 a-thujone reversed the increase induced by acute stress in the flunitrazepam-sensitive GABA(A) receptor recruitment. These findings demonstrated that a-thujone, when intracerebroventricularly administered, suppressed the GABA(A) receptor recruitment induced by acute stress, maybe due to a-thujone blocking the benzodiazepine binding site or another site of the GABA(A) complex. However, it should not be discarded that acute stress associated with novelty may have induced the recruitment of a subpopulation of GABA(A) receptors more sensitive to a-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 GABA(A) receptor. p-Thujone showed behavioural effects similar to its diastereoisomer a-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 GABA(A) receptor.
- 出版日期2014-3-25
