Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pregnant Sprague-Dawley rats were treated with 5 mg/kg body weight of phencyclidine (PCP) injected at 1 ml/kg subcutaneously on three consecutive days at four different stages of gestation. Within 10-30 min after treatment, dams showed some lack of motor coordination and became lethargic. On gestational day 21, all rats were killed by decapitation and brains were dissected and stored from mother and fetus for neurochemical analysis. PCP, dopamine and muscarinic cholinergic receptor binding was measured in membranes prepared from maternal and fetal whole brain. Neurotransmitter concentrations were also measured in the fetal brain homogenates. There was a significant decrease in PCP binding sites in fetal but not maternal brains after maternal PCP injection at gestational days 12-14, 15-17 and 18-20, but not at 9-11 days. Dopamine and muscarinic cholinergic receptor binding was not significantly altered in fetal or maternal brain when compared with vehicle control animals. The whole brain dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid concentrations did not show significant change in any group studied. These data indicate that gestational exposure to PCP decreases high affinity binding of PCP in term fetal brain at doses which do not alter maternal PCP receptor binding.
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PMID:Gestational exposure to phencyclidine (PCP) in rats decreases PCP binding sites in term fetal brain. 285 52

The venom of the parasitoid wasp Ampulex compressa induces long-lasting hypokinesia in the cockroach prey. Previous work indicates that the venom acts in the subesophageal ganglion to indirectly affect modulation of thoracic circuits for locomotion. However, the target of the venom in the subesophageal ganglion, and the mechanism by which the venom achieves its effects are as yet unknown. While the stung cockroaches appear generally lethargic, not all behaviors were affected, indicating that the venom targets specific motor systems and not behavior in general. Stung cockroaches were observed "freezing" in abnormal positions. Reserpine, which depletes monoamines, mimics the behavioral effects of the venom. We treated cockroaches with antagonists to dopamine and octopamine receptors, and found that the dopamine system is required for normal escape response. Dopamine injection induces prolonged grooming in normal cockroaches, but not in stung, suggesting that the venom is affecting dopamine receptors, or targets downstream of these receptors, in the subesophageal ganglion. This dopamine blocking effect fades slowly over the course of several weeks, similar to the time course of recovery from hypokinesia. The similarity in the time courses suggests that the mechanism underlying the hypokinesia may be the block of the dopamine receptors.
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PMID:Are monoaminergic systems involved in the lethargy induced by a parasitoid wasp in the cockroach prey? 1201 2

The parasitoid Jewel Wasp uses cockroaches as a live food supply for its developing larvae. The adult wasp uses mechanoreceptors on its stinger to locate the host's cerebral ganglia and injects venom directly into the cockroach's "brain," namely in the subesophageal ganglion and in and around the central complex in the supraesophageal ganglion. As a result, the cockroach first engages in continuous grooming for roughly 30 min. Dopamine identified in the wasp's venom is likely to cause this grooming, as injecting a dopamine-receptor antagonist into the cockroach hemolymph prior to a wasp's sting greatly reduced the venom-induced, excessive grooming. Conversely, injecting a dopamine-receptor agonist into the brain induces excessive grooming in normal cockroaches. A second effect of the head-sting is the induction of a long-lasting lethargic state, during which the cockroach demonstrates a dramatically reduced drive to self-initiate locomotion. Unlike most paralyzing venoms, Ampulex's venom seems to affect the "motivation" of its host to initiate locomotion, rather than affecting the motor centers directly. In fact, the venom specifically increases thresholds for the initiation of walking-related behaviors and, once such behaviors are initiated, affects their maintenance without affecting the walking-pattern generators. Thus, the venom manipulates neuronal centers within the cerebral ganglia that are specifically involved in the initiation and maintenance of walking. We have shown that in stung cockroaches focal injection of an octopaminergic receptor agonist around the central complex area in the brain partially restores walking. Another likely candidate target of the venom is the opioid system, which is known to affect responsiveness to stimuli in insects. Opioid receptor agonists increase startle threshold in control cockroaches and using a bioassay for opioid receptors, we found that the venom blocks opioid-like receptors. This effect is reversed with naloxone, an opioid antagonist.
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PMID:Wasp voodoo rituals, venom-cocktails, and the zombification of cockroach hosts. 2470 86