Functional magnetic resonance imaging studies of opioid receptor-mediated modulation of noxious-evoked BOLD contrast in rats.

RATIONALE: Functional magnetic resonance imaging (fMRI) in rats can non-invasively identify brain regions activated by physiological stimuli and the effects of pharmacological intervention on these responses. OBJECTIVES: This study was conducted to investigate the effects of systemic administration of the mu-opioid receptor agonist morphine on whole brain functional signal intensity in anaesthetised rats; to investigate whether pre-treatment with the opioid receptor antagonist naloxone blocks the effects of morphine; to determine whether pre-treatment with morphine attenuates noxious-evoked changes in whole brain functional signal intensity. METHODS: Continuous whole brain fMRI scanning was used to study brain signal intensity prior to, and following, systemic administration of morphine (5 mg/kg, n=7), systemic administration of naloxone (1 mg/kg) and morphine (n=8). Effects of pre-treatment with saline (n=5) or morphine (5 mg/kg, n=5) on formalin (5%, intraplantar)-evoked changes in signal intensity were determined. Data were processed using SMP99 with fixed-effects analysis (p<0.05). RESULTS: Morphine produced significant positive bilateral increases in signal intensity in the cingulate cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05), and these effects were blocked by naloxone. Intraplantar injection of formalin produced a significant positive increase in signal intensity in the cingulate cortex, somatosensory cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05). Morphine attenuated formalin-evoked increases in signal intensity in the PAG, amygdala, hypothalamus and cingulate cortex. CONCLUSION: Our data demonstrate that morphine modulates noxious-evoked changes in signal intensity in discrete brain regions. fMRI studies in rats are able to identify specific brain regions involved in the pharmacological modification of physiologically evoked changes in regional brain activation.

Methodological considerations in rat brain BOLD contrast pharmacological MRI.

RATIONALE AND OBJECTIVES: Blood oxygen level dependent (BOLD) contrast pharmacological magnetic resonance imaging (phMRI) is an increasingly popular technique that allows the non-invasive investigation of spatial and temporal changes in rat brain function in response to pharmacological stimulation in vivo. Rat brain BOLD contrast phMRI is, at present, established in few neuropharmacological laboratories, and various issues associated with the technique require attention. The present review is primarily aimed at psychopharmacologists with no previous experience of phMRI, who are interested in the practical aspects that phMRI studies entail. RESULTS AND DISCUSSION: Experimental and analytical considerations, including anaesthesia, physiological monitoring, drug dose and delivery, scanning protocols, statistical approaches and the interpretation of phMRI data, are discussed.

Dopamine antagonist modulation of amphetamine response as detected using pharmacological MRI.

Functional magnetic resonance imaging (fMRI), employing BOLD-contrast, was used to measure changes in regional brain activation following amphetamine administration, either alone or after pre-treatment with the dopamine D1 receptor antagonist SCH23390, or the dopamine D2 receptor antagonist, sulpiride, in anaesthetised rat. After obtaining baseline data, rats (n=8) were given amphetamine (3 g/kg i.v) and volume data sets collected for 90 mins. Acute amphetamine challenge caused widespread increases in BOLD signal intensity in many subcortical structures with rich dopaminergic innervation, with decreases in BOLD contrast observed in the superficial layers of the cortex. Pretreatment with SCH23390 (n=8, 0.5 mg/kg, i.v) substantially attenuated the increases in BOLD activity in response to amphetamine, with lesser effects on the amphetamine-evoked decreases in BOLD signal. In contrast, sulpiride (n=8, 50 mg/kg, i.v) predominantly blocked the decrease in BOLD signal, having a smaller effect on the increases in BOLD signal. In summary, these data are supportive of the notion that different dopamine receptor types are responsible for separate components of the full amphetamine response. Furthermore the utility of BOLD contrast fMRI as a means of characterising the mechanisms of drug action in the whole brain has been demonstrated. Such studies may be of particular use for investigation of localised action and interaction of different dopaminergic agents.

Detection of cannabinoid agonist evoked increase in BOLD contrast in rats using functional magnetic resonance imaging.

BOLD-contrast functional magnetic resonance imaging (fMRI) was used to investigate the effects of the synthetic cannabinoid agonist HU210 on the rat brain in order to determine potential CNS sites of action for the functional effects of cannabinoids. After obtaining basal data, rats (n=8) were given the cannabinoid agonist HU210 (10 microg/kg i.v.) and volume data sets collected for 85 mins. Significant increases in functional BOLD activity were observed in specific brain regions including those important in pain (PAG), reward (VTA and accumbens) and motor function (striatum). In order to confirm cannabinoid receptor involvement in the HU210 evoked functional BOLD activity, rats (n=8) were pre-treated with the CB1 cannabinoid receptor antagonist SR141716A (100 microg/kg i.v.) prior to HU210. Pretreatment with SR141716A abolished all significant evoked HU210 functional BOLD activity. To exclude the involvement of potential systemic effects induced by the cannabinoid agonist administration on the observed evoked functional BOLD activity a separate experiment investigated the effect of HU210 (10 microg/kg i.v.) on mean arterial pressure and showed that HU210 had no significant effect on pressure under chloral hydrate anaesthesia. In summary, this study demonstrates that the cannabinoid agonist HU210 evokes a significant increase in BOLD functional activity in specific regions and that this was cannabinoid receptor mediated. Furthermore the study indicates the potential value of fMRI in rodents to delineate pharmacologically induced changes in regional brain function.

Bacterial culture and sensitivity in pemphigus.

Infection is the commonest cause of death in pemphigus and the commonest infection is Staphylococcus aureus bacteremia. In present study bacterial culture and sensitivity from the lesion was done in 25 patients of pemphigus vulgaris and accordingly antibiotics were given along with other treatment of pemphigus i.e. steroid, immunosuppressive drug etc. Most common pathogenic bacteria isolated was Staphylococcus aureus and it was sensitive to cloxacillin, erythromycin, cefotaxime and lincomycin.

Langerhans cell histiocytosis.

A case of Langerhans Cell Histiocytosis (LCH) is reported in 1½ years old boy. He had seborrhoeic dermatitis like condition of scalp, papular lesions with purpura typical of Letterer-Siwe disease associated with constitutional symptoms, hepatosplenomegaly, jaundice, anaemia and thrombocytopenia. Peripheral blood film and bone marrow examination showed presence of LCH cells.

Bilateral pigmented hairy epidermal naevus.

A 15-year-old boy developed bilateral Becker's naevus over scapular region without any associated abnormality.

Perfluorodecanoic acid inactivation of a channel for 2-aminopurine in the L5178Y cell membrane and recovery of the channel.

Treatment of L5178Y mouse lymphoma cells with perfluoro-n-decanoic acid (PFDA) in growth medium for 24 hr at 30 degrees C produces a dose-dependent inactivation of a channel in the cell membrane. Activity of the channel was estimated from the initial rate of efflux of a fluorescent purine, 2-aminopurine (AP). The L5178Y cells were preloaded with 100 microM AP and excess AP was removed. The preloaded cells were put in a flow system, and AP efflux was estimated continuously at 21 degrees C from the fluorescence emission of AP at 370 nm. The AP channel was markedly inactivated by a treatment with 150 micrograms/ml PFDA for 24 hr at 30 degrees C. There was no significant recovery of AP flux after 3 days at 30 degrees C in fresh growth medium; however, recovery was significant after 6 days. Recovery of activity of the AP channel occurs in 1 day at 37 degrees C. The initial rate of AP efflux for control cells increases with AP concentration; the reaction is not saturated at 1000 microM AP. The efflux of AP was inhibited by the presence of uric acid in the external buffer. An apparent inhibition constant value of 355 microM was determined for urate inhibition of AP efflux. These observations suggest the presence of a urate-sensitive channel for AP in the membrane of L5178Y cells. The channel was inactivated by PFDA under conditions that had no significant effect on cell viability.