Iptakalim: A Potential Antipsychotic Drug with Novel Mechanisms?

Iptakalim is a novel putative adenosine triphosphate (ATP)-sensitive potassium (KATP) channel opener. In the brain, iptakalim is thought to act on the neuronal and astrocytic plasma membrane and/or mitochondrial KATP channels. Because iptakalim demonstrates an action on the regulation of dopamine and glutamate release in the forebrain regions, we examined its potential antipsychotic efficacy in several preclinical tests. First, we show that iptakalim is effective in reducing amphetamine- and phencyclidine-induced hyperlocomotion as well as selectively disrupting conditioned avoidance responding. Next, we show that combined iptakalim and amphetamine treatment produces a reduction on prepulse inhibition of acoustic startle and this combined drug effect is also found with haloperidol, but not with clozapine. Finally, we show that iptakalim and clozapine preferentially increase c-Fos expression in the medial prefrontal cortex, nucleus accumbens and lateral septal nucleus, whereas haloperidol induces a greater increase in the nucleus accumbens, the dorsolateral striatum and lateral septal nucleus. Collectively, our findings indicate that iptakalim is likely to be a potential antipsychotic drug with distinct mechanisms of action. This study also suggests that neuronal and astrocytic plasma membrane and/or mitochondrial KATP channels may be a novel target that deserves attention for antipsychotic drug development. Future research using other sensitive tests is needed to confirm this property of iptakalim.

An Evaluation of Diazacon as a Potential Contraceptive in Non-Native Rose-Ringed Parakeets

Rose-ringed parakeets (Psittacula krameri) have become widely established outside their native range through accidental or deliberate release. Potential economic impacts on agriculture, conservation concerns, and mixed public opinion regarding the species have highlighted the need to develop effective but humane management options. Fertility control might provide such a solution if a safe and environmentally benign contraceptive was available. The chemical 20,25-diazacholesterol dihydrochloride (diazacon) has previously been used to reduce reproductive output in avian species through reduction of blood cholesterol and cholesterol-dependent reproductive hormones. We orally dosed captive rose-ringed parakeets with a solution of either 9 mg/kg or 18 mg/kg of diazacon for up to 10 days and found that a dose of 18 mg/kg for 10 days temporarily reduced blood cholesterol levels with no adverse side effects. We evaluated this dose level in a captive population in semi-natural conditions during the 2008 breeding season and found a significant decrease in fertility. We concluded that diazacon has potential for fertility control in this species if a suitable formulation and delivery system is developed for free-living populations.

Potential Attractants for Detecting and Removing Invading Gambian Giant Pouched Rats (Cricetomys gambianus)

BACKGROUND: Native to Africa, Gambian giant pouched rats (Gambian rats; Cricetomys gambianus Waterh.) are a threatening invasive species on a Florida island, Grassy Key. Gambian giant pouched rats shifted from a domestic pet to invading species after suspected release from a pet breeder. Because of the large size of Gambian rats (weighing up to 2.8 kg), they pose a serious threat to native species (particularly nesting species) and agricultural crops, especially if Gambian rats invade mainland Florida. Also, Gambian rats pose a threat from disease, as they were implicated in a monkeypox outbreak in the mid-western United States in 2003. The United States Department of Agriculture’s Wildlife Services has initiated eradication and detection efforts in the Florida Keys, but trapping the sparse population of Gambian rats has proven difficult. RESULTS: Fifteen attractants that could be used in traps for capturing or detecting single or paired Gambian rats were tested. It was found that conspecific scents (i.e. feces and urine) from other Gambian rats were the best treatment for attracting single and paired Gambian rats. Single Gambian rats explored more attractant types than paired Gambian rats. CONCLUSIONS: Effective attractants for use with Gambian rats have been identified, and multiple attractant types should be used to capture or detect the sparse population. It is recommended that mainly urine and feces from Gambian rats be used, but peanut butter, anise, ginger and fatty acid scent could also be useful for attracting the currently small population of Gambian rats on Grassy Key.