Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jan 2012
Comparative StudyCombined α7 nicotinic acetylcholine receptor agonism and partial serotonin transporter inhibition produce antidepressant-like effects in the mouse forced swim and tail suspension tests: a comparison of SSR180711 and PNU-282987.
Emerging evidence points to an involvement of nicotinic acetylcholine receptors (nAChRs) in major depression. Nicotine improves symptoms of depression in humans and shows antidepressant-like effects in rodents. Monoamine release is facilitated by nAChR stimulation, and nicotine-evoked serotonin (5-HT) release has been shown to depend on α7 nAChR activation. ⋯ This suggests that the antidepressant-like activity of SSR180711 may involve partial 5-HT reuptake inhibition. SSR180711 therefore represents a compound displaying the synergistic effect of α7 nAChR agonism combined with partial 5-HT reuptake inhibition previously described. The addition of α7 nAChR agonism to classical monoamine-based mechanisms may represent a novel option for the improved treatment of major depression.
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Pharmacol. Biochem. Behav. · Jan 2012
Characterizing the behavioral effects of nerve agent-induced seizure activity in rats: increased startle reactivity and perseverative behavior.
The development and deployment of next-generation therapeutics to protect military and civilian personnel against chemical warfare nerve agent threats require the establishment and validation of animal models. The purpose of the present investigation was to characterize the behavioral consequences of soman (GD)-induced seizure activity using a series of behavioral assessments. Male Sprague-Dawley rats (n=24), implanted with a transmitter for telemetric recording of encephalographic signals, were administered either saline or 1.0 LD₅₀ GD (110 μg/kg, sc) followed by treatment with a combination of atropine sulfate (2 mg/kg, im) and the oxime HI-6 (93.6 mg/kg, im) at 1 min post-exposure. ⋯ Animals that experienced GD-induced seizure activity engaged in perseverative food trough-directed behaviors. There were few differences between groups on other measures of FR schedule-controlled behavior. It is concluded that the GD-induced seizure activity increased startle reactivity and engendered perseverative responding and that these measures are useful for assessing the long-term effects of GD exposure in rats.
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Pharmacol. Biochem. Behav. · Jan 2012
Randomized Controlled Trial Clinical TrialSubjective, psychomotor, and physiological effects of pregabalin alone and in combination with oxycodone in healthy volunteers.
Pregabalin is an anticonvulsant drug indicated for neuropathic disorders and fibromyalgia. Some chronic pain patients suffering from these disorders take both this drug and an opioid for pain relief. Pregabalin is a scheduled drug under the Controlled Substances Act. ⋯ When 75 mg pregabalin was combined with oxycodone some subjective effects were altered relative to placebo, in contrast to when each drug was tested alone. Liking of oxycodone was not increased by 75 mg pregabalin. However, recent studies have suggested that this drug is abused, and we would recommend that further psychopharmacological studies with pregabalin are warranted, including a study assessing its abuse liability across a range of doses in sedative abusers.
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Pharmacol. Biochem. Behav. · Jan 2012
Comparative StudyEffects of oral loperamide on efficacy of naltrexone, baclofen and AM-251 in blocking ethanol self-administration in rats.
Naltrexone is a μ-opioid receptor antagonist that has been extensively studied for its ability to block the rewarding effects of ethanol. Opioid receptors are widely distributed within the gastrointestinal tract (GIT). Typically, naltrexone is administered by parenteral routes in nonclinical studies. ⋯ Finally, the specific opioid receptor type involved was investigated using selective μ- and κ-receptor antagonists to determine if these would affect the ability of the AM-251 and loperamide combination to block ethanol drinking behavior. The effect of loperamide was blocked by ALKS 37, a peripherally restricted μ-receptor antagonist. These data suggest an important role for opioid receptors within the GIT in modulating central reward pathways and may provide new insights into strategies for treating reward disorders, including drug dependency.
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Pharmacol. Biochem. Behav. · Jan 2012
S14G-humanin improves cognitive deficits and reduces amyloid pathology in the middle-aged APPswe/PS1dE9 mice.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by clinical cognitive decline and pathological deposition of amyloid-beta protein (Aβ) in the brain. So far, there has been no causative therapy for this devastating disease. S14G-Humanin (HNG), a synthetic derivative of Humanin (HN), has been shown to have strong neuroprotective ability against AD-related insults in vitro and prevent cognitive impairments in Aβ-infused animal models. ⋯ We found that vehicle-treated APPswe/PS1dE9 mice showed impaired spatial learning and memory compared with vehicle- and HNG-treated wild-type mice, while intraperitoneal HNG treatment for 3 months significantly improved spatial learning and memory deficits in APPswe/PS1dE9 mice compared with vehicle control treatment. Coincidental with this, HNG treatment significantly reduced cerebral Aβ plaque deposition, insoluble Aβ levels, and neuroinflammatory responses in APPswe/PS1dE9 mice compared with control treatment. Cumulatively, these findings demonstrate that chronic administration of HNG is able to attenuate cognitive deficits and reduce Aβ loads as well as neuroinflammation in the middle-aged APPswe/PS1dE9 mice even with pre-existing substantial Aβ neuropathology, indicating that HNG has potential as a pharmacotherapeutic intervention in the development of cognitive deficits and neuropathology seen in the cases of established AD.