Stimulation of central 5-HT1D receptors causes hypothermia in the guinea-pig

The 5-HT(1) receptor agonist GR46611 (3-30 mg/kg s.c.) caused a dose-related decrease in rectal temperature in the adult guinea-pig. A lower dose (20 μg) administered directly into the lateral cerebral ventricle also caused a hypothermic response, suggesting that this effect is centrally mediated. GR46611-induced (10 mg/kg s.c.) hypothermia was not attenuated by WAY100135 (3-10 mg/kg s.c.), ritanserin (0.3-1 mg/kg s.c.), spiperone (0.1-0.3 mg/kg s.c.) and ondansetron (0.1-1 mg/kg s.c.), suggesting that 5-HT(1A), 5-HT(2A), 5-HT( 2C) and 5-HT(3) receptors are unlikely to be involved in this response. In contrast, the poorly selective 5-HT receptor antagonist, metergoline (1-10 mg/kg s.c.), and the potent 5-HT(1D) receptor antagonist, GR127935 (0.1-1 mg/kg p.o.), antagonized the effects of GR46611. The present data suggest that antagonism of GR46611-induced hypothermia may be useful for assessing the potency and duration of action of centrally-acting 5-HT( 1D) receptor antagonists in the guinea-pig.     

Differences between three rat strains in sensitivity to prepulse inhibition of an acoustic startle response: influence of apomorphine and phencyclidine pretreatment

In the present study we have examined the effect of varying three prepulse parameters (prepulse intensity, prepulse duration, prepulse-pulse interval) on the level of prepulse inhibition (PPI) in Lister hooded, Wistar and Sprague-Dawley rats. The results indicate that each strain showed subtle differences in sensitivity to the prepulse. For instance, Sprague-Dawley and Lister hooded rats showed PPI to prepulses of lower saliency compared to Wistar rats. Optimal prepulse parameters were selected for each strain to examine the effects of apomorphine and phencyclidine on PPI. Further inter-strain differences were noted; apomorphine (0.1-1 mg/kg) increased startle amplitude in Lister hooded and Sprague-Dawley, but not Wistar rats. PPI was attenuated in each strain by apomorphine pretreatment. In a final series of experiments, phencyclidine disrupted PPI in each strain, although with greater potency in the Lister hooded rats. A marked behavioural syndrome was seen at phencyclidine doses that disrupted PPI. It is concluded that rat strain and prepulse parameters are important variables in studying drug effects on PPI.     

Release and actions of adenosine in the central nervous system

Adenosine is released from active neurons into the extracellular fluid at a concentration of about 1mol/l. Neither the precise cellular origin nor the biochemical form of release has been firmly established, though the nucleotide is probably released partly directly, as a result of raised intracellular levels, and partly as nucleotides, which are subsequently hydrolysed. Once in the extracellular medium, adenosine markedly inhibits the release of excitatory neurotransmitters and modulatory peptides and has direct inhibitory effects on postsynaptic excitability via A₁ receptors. A population of A₂ receptors may mediate depolarization and enhanced transmitter release. Adenosine also modulates neuronal sensitivity to acetylcholine and catecholarnines, all these effects probably contributing to the behavioural changes observed in conscious animals. As a result of their many actions, adenosine analogues are being intensively investigated for use as anticonvulsant, anxiolytic, and neuroprotective agents.     

4S

A dramatic increase in the number of niche drugs with smaller markets may result from the sequencing of the human genome. As the information flow from this project speeds up, a number of pharmaceutical industry watchers are predicting this and other profound changes. Another likely effect is a reduction in basic research costs, but also a concomitant drop in profits from individual drugs.     

Effects of response cost and unit dose on alcohol self-administration in moderate drinkers

Alcohol self-administration by nonhumans and alcoholic humans decreases as the response requirement to obtain the drug increases. Also, increases in dose or concentration of alcohol, increase consumption up to a maximum in these populations, after which further increases in dose decrease intake. In the present study, the effects of response cost and dose on alcohol self-administration were investigated in moderate drinkers (12-45 drinks/week). Three male volunteers self-administered alcohol (commercial beer) during 2h sessions twice weekly. Alcohol was available under a fixed-ratio (FR) schedule of reinforcement. Response requirement (FR100-1600) and dose (2 and 4oz of beer) were varied separately across sessions using a within-subjects design. As response cost increased, consumption and overall rates of responding generally changed in an inverted U-shaped manner. Maximal consumption was observed at the 4oz dose. These orderly relations between response cost, dose and alcohol self-administration extend prior findings in nonhumans and alcoholics to moderate drinkers. Such consistencies support a position that a common set of variables control alcohol self-administration across these populations.     

Awake oral fibreoptic intubation for caesarean section

A 35-week pregnant patient with ankylosing spondylitis and a known previous failed intubation required an elective caesarean section for intrauterine growth retardation. Regional anaesthesia was prevented by extensive spinal fusion. The anaesthetic management involved an awake oral fibreoptic intubation followed by induction and maintenance of general anaesthesia allowing delivery of a live infant without harm to the mother.     

Leading physicians into the new millennium. MSMS introduces new services to meet members changing needs

The challenges in the practice of medicine change every day. Physicians are looking for ways to meet those challenges with effective, cost-efficient, and high quality resources that improve their practices, yet protect their relationships with their patients. MSMS has responded to physicians' needs with an array of cutting edge.     

Expression of the insecticidal bean alpha-amylase inhibitor transgene has minimal detrimental effect on the nutritional value of peas fed to rats at 30% of the diet.

The effect of expression of bean alpha-amylase inhibitor (alpha-AI) transgene on the nutritional value of peas has been evaluated by pair-feeding rats diets containing transgenic or parent peas at 300 and 650 g/kg, respectively, and at 150 g protein/kg diet, supplemented with essential amino acids to target requirements. The results were also compared with the effects of diets containing lactalbumin with or without 0.9 or 2.0 mg bean alpha-AI, levels equivalent to those in transgenic pea diets. When 300 and 650 g peas/kg diet were fed, the daily intake of alpha-AI was 11.5 or 26.3 mg alpha-AI, respectively. At the 300 g/kg level, the nutritional value of the transgenic and parent line peas was not significantly different. The weight gain and tissue weights of rats fed either of the two pea diets were not significantly different from each other or from those of rats given the lactalbumin diet even when this was supplemented with 0.9 g alpha-AI/kg. The digestibilities of protein and dry matter of the pea diets were slightly but significantly lower than those of the lactalbumin diet, probably due to the presence of naturally occurring antinutrients in peas. The nutritional value of diets containing peas at the higher (650 g) inclusion level was less than that of the lactalbumin diet. However, the differences between transgenic and parent pea lines were small, possibly because neither the purified recombinant alpha-AI nor that in transgenic peas inhibited starch digestion in the rat small intestine in vivo to the same extent as did bean alpha-AI. This was the case even though both forms of alpha-AI equally inhibited alpha-amylase in vitro. Thus, this short-term study indicated that transgenic peas expressing bean alpha-AI gene could be used in rat diets at 300 g/kg level without major harmful effects on their growth, metabolism and health, raising the possibility that transgenic peas may also be used at this level in the diet of farm animals.