Effects of selected opioid agonists and antagonists on DMT-and LSD-25-induced disruption of food-rewarded bar pressing behavior in the rat

Several opioid agonists and antagonists interact with N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) in adult male Holtzman rats trained on a positive reinforcement, fixed ratio 4 (FR 4 ) behavioral schedule, i.e., a reward of 0.01 ml sugar-sweetened milk was earned on every fourth bar press. DMT (3.2 and 10.0 mg/kg) and LSD (0.1 mg/kg) given IP with 0.9% NaCl pretreatment, disrupted food-rewarded FR4 bar pressing. Animals were pretreated IP (10–15 min) with predetermined, behaviorally noneffective doses of morphine, methadone, naltrexone, and the (+)-and (-)-enantiomers of naloxone prior to receiving DMT or LSD. Dose-dependent effects were shown with opioid agonist pretreatment. Morphine (0.32–1.0 mg/kg) and methadone (0.32 mg/kg) significantly antagonized the bar pressing disruption induced by DMT and LSD. Larger doses of morphine (3.2 mg/kg) and methadone (1.0–3.2 mg/kg) potentiated only LSD-induced effects, with no effect on DMT-treated groups. The opioid antagonists (-)-naloxone and naltrexone potentiated the disruption of bar pressing induced by DMT and LSD. Failure of (+)-naloxone to potentiate the DMT effects was attributed to a stereospecific opioid antagonist effect of (-)-naloxone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46425/1/213_2004_Article_BF00432428.pd

Aphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) in male mice: a comparative study

BACKGROUND: Spices are considered as sexual invigorators in the Unani System of Medicine. In order to explore the sexual function improving effect of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) an experimental study was conducted in normal male mice. METHODS: The extracts (50% ethanolic) of nutmeg and clove were administered (500 mg/kg; p.o.) to different groups of male Swiss mice. Mounting behaviour, mating performance, and general short term toxicity of the test drugs were determined and compared with the standard drug Penegra (Sildenafil citrate). RESULTS: The extracts of the nutmeg and clove were found to stimulate the mounting behaviour of male mice, and also to significantly increase their mating performance. The drugs were devoid of any conspicuous general short term toxicity. CONCLUSION: The extracts (50% ethanolic) of nutmeg and clove enhanced the sexual behaviour of male mice

Effects of apomorphine on elicited and operant pecking in pigeons

The effects of apomorphine (0.001–32.0 mg/kg) on elicited and operant pecking were studied in pigeons. Elicited pecking was measured in a 1-h observation test. Apomorphine caused dose-related increases in the pecking elicited by the drug in all the subjects, with maximal responding at 3.2 mg/kg. In contrast, operant responding on a multiple, 5 min fixed interval, 30 response fixed-ratio schedule revealed individual differences in sensitivity to the drug. A dose of 0.32 mg/kg eliminated key pecking in fixed-interval and fixed-ratio components in 4 (group 1) of the 15 subjects while 3.2 mg/kg eliminated responding in 9 other subjects (group 2), and 2 of the subjects (group 3) required 32.0 mg/kg to eliminate responding. The 13 birds in groups 1 and 2 showed decreases in operant responding with concomitant increases in elicited pecking. For the 2 remaining birds, increases in operant behavior were highly correlated with increased stereotypy. The effects of apomorphine on operant behavior appeared to depend on induced stereotypy, with rate-decreasing effects resulting from the disruption of ongoing behavior by stereotyped pecking aimed else-where in the chamber, and rate increases resulting from the redirection of elicited pecking towards the operant key.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46420/1/213_2004_Article_BF00433057.pd

Incidence, mechanism and prognostic value of activated AKT in pancreas cancer

When activated, the serine/threonine kinase AKT mediates an antiapoptotic signal implicated in chemoresistance of various cancers. The mechanism(s) of AKT activation are unknown, though overexpression of HER-2/neu has been implicated in breast cancer. Therefore, we determined the incidence of activated AKT in human pancreatic cancer, whether HER-2/neu is involved in AKT activation, and if AKT activation is associated with biologic behaviour. HER-2/neu expression and AKT activation were examined in seven pancreatic cancer cell lines by Western blotting. The in vitro effect of HER-2/neu inhibition on AKT activation was similarly determined. Finally, 78 pancreatic cancer specimens were examined for AKT activation and HER-2/neu overexpression, and correlated with the clinical prognostic variable of histologic grade. HER-2/neu was overexpressed in two of seven cell lines; these two cell lines demonstrated the highest level of AKT activation. Inhibition of HER-2/neu reduced AKT activation in vitro. AKT was activated in 46 out of 78 (59%) of the pancreatic cancers; HER-2/neu overexpression correlated with AKT activation (P=0.015). Furthermore, AKT activation was correlated with higher histologic tumour grade (P=0.047). Thus, it is concluded that AKT is frequently activated in pancreatic cancer; this antiapoptotic signal may be mediated by HER-2/neu overexpression. AKT activation is associated with tumour grade, an important prognostic factor

Screening of Tanzanian medicinal plants for anti-Candida activity

BACKGROUND: Candida albicans has become resistant to the already limited, toxic and expensive anti-Candida agents available in the market. These factors necessitate the search for new anti-fungal agents. METHODS: Sixty-three plant extracts, from 56 Tanzanian plant species obtained through the literature and interviews with traditional healers, were evaluated for anti-Candida activity. Aqueous methanolic extracts were screened for anti-Candida activity by bioautography agar overlay method, using a standard strain of Candida albicans (ATCC 90028). RESULTS: Twenty- seven (48%) out of the 56 plants were found to be active. Extracts of the root barks of Albizia anthelmintica and Balanites aegyptiaca, and roots of Plectranthus barbatus showed strong activity. CONCLUSION: The extracts that showed strong anti-Candida activity are worth of further investigation in order to isolate and identify the active compounds

Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists

It has now been demonstrated that the μ, δ(1), δ(2), and κ(1) opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct‐reducing effect with prophylactic administration and prevent reperfusion‐induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena. Furthermore, opioids are also effective in preventing ischemia‐induced arrhythmias

Differential Pharmacological Actions of Methadone and Buprenorphine in Human Embryonic Kidney 293 Cells Coexpressing Human μ-Opioid and Opioid Receptor-Like 1 Receptors

Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human μ-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors

Effect of photosynthetic photon flux density on growth, photosynthetic competence and antioxidant enzymes activity during ex vitro acclimatization of Dieffenbachia cultivars

The effects of 35, 70 and 100 µmol m−2 s−1 photosynthetic photon flux density (PPFD) were investigated on ex vitro acclimatization of micropropagated Dieffenbachia plants. Various growth characteristics, photosynthetic parameters and activities of antioxidant enzymes and dehydrins (DHN) were investigated. Fresh and dry plant biomass, plant height and root length were highest under the highest PPFD (100 µmol m−2 s−1), but this treatment was responsible for a reduction in the number of leaves. Chlorophyll and carotenoid contents and net photosynthesis were also optimal in plants grown under the highest irradiance. Stomatal resistance, transpiration rate and Fv/Fm values decreased with the incremental light irradiance. Activities of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were higher in the plants treated with 70 and 100 µmol m−2 s−1 PPFD. Accumulation of 55 kDa, 40 and 22 kDa DHN was observed in all light treatments. These results depict that lower PPFD (35 µmol m−2 s−1) was suitable for acclimatization of Dieffenbachia plants. High PPFD (>70 µmol m−2 s−1) induced accumulation of antioxidants and accumulation of DHN in the plants which reveals enhanced stress levels