SUMMARYInsect ecdysis sequence is composed of pre-ecdysis, ecdysis and post-ecdysis behaviors controlled by a complex cascade of peptide hormones from endocrine Inka cells and neuropeptides in the central nervous system (CNS). Inka cells produce pre-ecdysis and ecdysis triggering hormones (ETH) which activate the ecdysis sequence through receptor-mediated actions on specific neurons in the CNS. Multiple experimental approaches have been used to determine mechanisms of ETH expression and release from Inka cells and its action on the CNS of moths and flies. During the preparatory phase 1-2 days prior to ecdysis, high ecdysteroid levels induce expression of ETH receptors in the CNS and increased ETH production in Inka cells, which coincides with expression of nuclear ecdysone receptor (EcR) and transcription factor cryptocephal (CRC). However, high ecdysteroid levels prevent ETH release from Inka cells. Acquisition of Inka cell competence to release ETH requires decline of ecdysteroid levels and β-FTZ-F1 expression few hours prior to ecdysis. The behavioral phase is initiated by ETH secretion into the hemolymph, which is controlled by two brain neuropeptides -corazonin and eclosion hormone (EH). Corazonin acts on its receptor in Inka cells to elicit low level ETH secretion and initiation of pre-ecdysis, while EH induces cGMP-mediated ETH depletion and consequent activation of ecdysis. The activation of both behaviors is accomplished by ETH action on central neurons expressing ETH receptors A and B (ETHR-A and B). These neurons produce numerous excitatory or inhibitory neuropeptides which initiate or terminate different phases of the ecdysis sequence. Our data indicate that insect ecdysis is a very complex process characterized by two principal steps: 1) Ecdysteroid-induced expression of receptors and transcription factors in the CNS and Inka cells. 2) Release and interaction of Inka cell peptide hormones and multiple central neuropeptides to control consecutive phases of the ecdysis sequence.

SUMMARYPre-ecdysis- and ecdysis-triggering hormones (PETH and ETH) from endocrine Inka cells initiate ecdysis in moths and Drosophila through direct actions on the central nervous system (CNS). Using immunohistochemistry, we found Inka cells in representatives of all major insect orders. In most insects, Inka cells are numerous, small and scattered throughout the tracheal system. Only some higher holometabolous insects exhibit 8-9 pairs of large Inka cells attached to tracheae in each prothoracic and abdominal segment. The number and morphology of Inka cells can be very variable even in the same individuals or related insects, but all produce peptide hormones that are completely released at each ecdysis. Injection of tracheal extracts prepared from representatives of several insect orders induces pre-ecdysis and ecdysis behaviours in pharate larvae of Bombyx, indicating functional similarity of these peptides. We isolated several PETH-immunoreactive peptides from tracheal extracts of the cockroach Nauphoeta cinerea and the bug Pyrrhocoris apterus and identified the gene encoding two putative ETHs in the mosquito Anopheles gambiae. Inka cells also are stained with antisera to myomodulin, FMRFamide and other peptides sharing RXamide carboxyl termini. However, our enzyme immunoassays show that these antisera cross-react with PETH and ETH. Our results suggest that Inka cells of different insects produce only peptide hormones closely related to PETH and ETH, which are essential endocrine factors required for activation of the ecdysis behavioural sequence.

The management of schizophrenia is generally a long-term process with neuroleptics representing the cornerstone of treatment. Although not without their own limitations, depot neuroleptics offer an important alternative to oral agents, and they should be routinely considered as an option in any long-term treatment planning. The present article reviews depot neuroleptics, and focuses particularly on clinical considerations pertaining to their use.

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