Chronic neuroleptic-induced mouth movements in the rat: suppression by CCK and selective dopamine D1 and D2 receptor antagonists

Fluphenazine decanoate (25 mg/kg IM every 3 weeks x 6) resulted in spontaneous vacuous chewing mouth movements and jaw tremor in male Sprague-Dawley rats. These movements could be suppressed by the selective D1 or D2 dopamine antagonists SCH 23390 (0.5 mg/kg) and raclopride (0.5 mg/kg), respectively, and by CCK-8S (50 g/kg). Fluphenazine-induced mouth movements were unaffected by the selective CCK antagonist MK-329, and by a dose of physostigmine (50 g/kg) sufficient to stimulate mouth movements in placebo treated rats. Scopolamine (0.1 mg/kg) suppressed spontaneous mouth movements in placebo-treated rats, but the effect on fluphenazine-induced mouth movements was not significant. A higher dose of scopolamine (0.5 mg/kg) did suppress the neuroleptic-induced mouth movements, but also induced hyperactivity, characterized by increased sniffing and grooming. These findings indicate that mouth movements resulting from the chronic administration of neuroleptics to the rat may serve as a useful pharmacological model of tardive dyskinesia in the human, and suggest that a relative increase of D1 activity as well as impaired CCK function may contribute to the pathogenesis of this disorder.     

Outbreak of Shigella sonnei infection traced to imported iceberg lettuce.

In the period from May through June 1994, an increase in the number of domestic cases of Shigella sonnei infection was detected in several European countries, including Norway, Sweden, and the United Kingdom. In all three countries epidemiological evidence incriminated imported iceberg lettuce of Spanish origin as the vehicle of transmission. The outbreaks shared a number of common features: a predominance of adults among the case patients, the presence of double infections with other enteropathogens, and the finding of two dominant phage types among the bacterial isolates. In Norway 110 culture-confirmed cases of infection were recorded; more than two-thirds (73%) were adults aged 30 to 60 years. A nationwide case-control study comprising 47 case patients and 155 matched control individuals showed that the consumption of imported iceberg lettuce was independently associated with an increased risk of shigellosis. Epidemiological investigation of a local outbreak incriminated iceberg lettuce from Spain, consumed from a salad bar, as the source. The presence of shigellae in the suspected food source could not be documented retrospectively. However, high numbers of fecal coliforms were detected in iceberg lettuce from patients' homes. Three lettuce specimens yielded salmonellae. The imported iceberg lettuce harbored Escherichia coli strains showing resistance to several antimicrobial agents, including ampicillin, ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole. During the outbreak it is likely that thousands of Norwegians and an unknown number of consumers in other countries were exposed to coliforms containing antibiotic resistance genes.     

Linoleic acid and dihomogammalinolenic acid inhibit leukotriene B4 formation and stimulate the formation of their 15-lipoxygenase products by human neutrophilsin vitro. Evidence of formation of antiinflammatory compounds

Enzymatic transformation of then-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) by the 5-lipoxygenase (LO) enzyme results in the formation of leukotrienes (LTs) including leukotriene B₄ (LTB₄), which is a potent mediator of inflammation. The purpose of the present study was to determine the effect of othern-6 fatty acids on the formation of LTB₄ by human neutrophils and to determine if thesen-6 fatty acids themselves may be transformed into products with antiinflammatory capacity. Purified neutrophils isolated from heparinized human venous blood were incubated with A23187 (5 M) and different concentrations (0–100 M) of then-6 fatty acids linoleic acid (LA) and dihomo-gammalinolenic acid (DGLA). LO products were determined by use of quantitative reversed-phase high performance liquid chromatography (RP-HPLC) and mass spectrometry. The formation of LTB₄ was dose dependently inhibited by both LA (IC₅₀=45 M) and DGLA (IC₅₀=40M). This inhibition of LTB₄ formation was associated with a dose dependent increase in the formation of the respective 15-LO products of LA (13-hydroxy-octadecadienoic acid; 13-HODE) and DGLA (15-hydroxy-eicosatrienoic acid; 15-HETrE). To determine whether these 15-LO products themselves might inhibit LTB₄ formation, neutrophils were incubated with 13-HODE and 15-HETrE. Both 15-LO products lead to a dose-dependent inhibition of LTB₄ formation (IC₅₀=7.5 M and IC₅₀=0.2 M). For comparison the 15-LO product of AA, 15-hydroxy-eicosatetraenoic acid (15-HETE), also inhibited LTB₄ formation (IC₅₀=0.75 M). The results show that the addition of LA and DGLA to neutrophils results in an inhibition of LTB₄ formation and simultaneously to the formation of 13-HODE and 15-HETrE, that also inhibits LTB₄ formation. Therefore, dietary supplementation or topical application of LA and DGLA or preferentially their respective 15-LO products, may have a therapeutic effect in inflammatroy diseases in which LTs are suspected to play a pathogenic role.     

The role of post-synaptic neurones in the biochemical maturation of presynaptic cholinergic nerve terminals in a mouse sympathetic ganglion

1. The role of post-synaptic adrenergic neurones in the biochemical maturation of presynaptic cholinergic nerve terminals has been investigated in mouse superior cervical ganglion in vivo.2. Selective destruction of ganglion adrenergic neurones chemically, with 6-hydroxydopamine (6-OH-DA), or immunologically, with nerve growth factor antiserum (NGF-antiserum) prevented the normal maturation of choline acetyl transferase (ChAc) activity in presynaptic endings during development. Enzyme activity remained depressed for at least 2 months.3. 6-OH-DA treatment failed to alter ChAc activity in the developing duodenum or diaphragm, organs in which cholinergic fibres do not synapse with adrenergic neurones, suggesting that destruction of post-synaptic neurones per se inhibited presynaptic maturation.4. Similarly, NGF-antiserum, which does not destroy adrenergic neurones in the adult did not alter ChAc activity in adult mouse ganglia.5. These observations suggest that post-synaptic adrenergic neurones regulate the biochemical development of presynaptic cholinergic nerve terminals.     

Selective cytotoxic lesions of the retrohippocampal region produce a mild deficit in social recognition memory

Although a number of studies have implicated the hippocampal formation in social recognition memory in the rat, a recent study in this laboratory has demonstrated that selective cytotoxic lesions, confined to the hippocampus proper (encompassing the four CA subfields and the dentate gyrus), are without effect on this behaviour. This finding suggests that the hippocampus proper does not subserve social recognition memory in the rat, but does not preclude the possibility that other areas of the hippocampal formation, such as the entorhinal cortex or subiculum, could support this form of learning. The present study addressed this issue by examining the effects of selective cytotoxic retrohippocampal (RHR) lesions (including both the entorhinal cortex and subiculum) on social recognition memory in the rat. RHR lesions produced a mild social recognition memory impairment, although lesioned animals still displayed a reduction in investigation time between the first and second exposure to the juvenile. This result is consistent with other studies which have implicated the retrohippocampal or parahippocampal area in olfactory recognition memory processes. It also suggests, however, that other areas, out with the retrohippocampal region, are also likely to play an important role in social recognition memory.     

EEG-Monitored ECT: A Comparison of Seizure Duration under Anesthesia with Etomidate and Thiopentone

Electroencephalogram-monitored electroconvulsive therapy (ECT) was carried out in 20 depressed inpatients. Before treatment, patients were randomly allocated to treatment using etomidate (Hypnomidat) (n = 10) or thiopentone (n = 10) for anesthesia. The groups were matched for sex, age, weight, and type and severity of depression. The seizure duration (seconds) was measured by electroencephalography (EEG), and the electrical energy (Joules, J) was determined for each treatment. A ratio of seizure duration:electrical energy (s/J) was computed. Both seizure duration and seizure duration:electrical energy were greater in the etomidate group than in the thiopentone group, whereas electrical energy did not differ significantly. The number of treatments in the etomidate group did not differ from that in the thiopentone group, as may be expected, perhaps because of the small size.     

Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis

1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract.
2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis.
3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME 30 mg kg⁻¹). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions.
4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.

     

Venous plasma levels of endothelin-1 are not altered immediately after nitroglycerin infusion in healthy subjects

Endothelin-1 and nitric oxide play an important regulatory role in the control of vascular smooth muscle tone. Nitroglycerin (NTG), a nitric oxide donating drug, may inhibit endothelin production. In this double-blind placebo-controlled crossover study, plasma levels of endothelin-1 were measured before and immediately (5–30 s) after 80 min infusion of NTG (glyceryl trinitrate) or saline in 12 healthy subjects. On two different days separated by at least 1 week, NTG in four different doses, 0.015, 0.25, 1.0, and 2.0 g·kg^–1·min^–1, or placebo (isotonic saline) was infused successively for 20 min each dose. During the infusion blood pressure and heart rate were measured. NTG infusion significantly decreased systolic blood pressure from 112.4 to 103.4 mmHg and pulse pressure from 39.3 to 29.5 mmHg. Heart rate increased from 62.7 to 73.1 beats·min^–1. No changes in endothelin-1 plasma levels were induced by NTG infusion (2.4 pg·ml^–1 before NTG vs. 2.7 pg·ml^–1 after NTG) and placebo infusion also did not affect plasma endothelin-1. It is concluded that venous plasma levels of endothelin-1 are not altered immediately after NTG infusion.