Animal models of anxiety: an ethological perspective

In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanism underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABAA receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT1A receptor ligands, and panicolytic/panicogenic agents. On the basis of this review, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail.     

Hormonal correlates of environmentally induced metamorphosis in the Western spadefoot toad, Scaphiopus hammondii

An elaborate network of transmitter receptors, synapse associated proteins (SAPs), and cytoskeletal elements, generally known as the postsynaptic density, is involved with efficient synaptic signaling. The localization of the synapse associated protein SAP102 was studied in the rat retina by using immunocytochemical methods. Immunofluorescence for SAP102 was most prominent in the inner plexiform layer (IPL). It had a punctate appearance, suggesting a synaptic clustering of SAP102 in the IPL. Electron microscopy by use of pre-embedding immunocytochemistry showed that SAP102 is concentrated in the IPL in processes which are postsynaptic at bipolar cell ribbon synapses (dyads). As a rule, only one of the two postsynaptic members of the dyad was labeled for SAP102. Double-labeling experiments were performed in order to find out whether SAP102 is involved with the clustering the N-methyl-D-aspartate (NMDA) receptor 2A subunit (NR2A). Only a fraction (approximately 23%) of the SAP102 clusters expressed NR2A, suggesting SAP102 is also associated with other subunits or receptors. Distinct SAP102 labeling was also present in horizontal cell processes in the outer plexiform layer (OPL), which are inserted as lateral elements into photoreceptor ribbon synapses (triads). The optic nerve fibre layer was also diffusely immunoreactive for SAP102. The postsynaptic aggregation of SAP102 at bipolar cell dyads and at photoreceptor triads suggests SAP102 is associated with the clustering of transmitter receptors. However, the labeling of the optic nerve fibre layer indicates additional functions of SAP102 in the retina.     

Targeting technologies--recent patent literature

The patent literature is rich with information about ideas and approaches related to targeted drug delivery. Although there is a typically a delay in the release of this information compared to that published in journal articles, some of the subject matter of patent applications is never released through any other medium and the breadth of anticipated uses is described best in the patent literature. As with any form of information, the patent literature can only provide an historical perspective of what has already occurred. However, the trends of this literature clearly points to the possibilities for the future in drug targeting.     

Rapid growth problems: ascites and skeletal deformities in broilers

Over the last 40 yr, genetic selection for rapid growth and improved feed efficiency has been very effective in meat-type poultry. Combined with changes in the feed that have increased both the nutritional and physical density to encourage a high nutrient intake, growth rate has more than doubled. The effect of genetic selection for high muscle to bone ratio and high calorie intake of a ration that supplies all nutritional requirements causes significant mortality from cardiovascular disease. In the chicken, sudden death syndrome (flip-over) and pulmonary hypertension syndrome resulting in ascites are the most important. Ruptured aorta, spontaneous turkey cardiomyopathy (round heart), and cardiomyopathy causing sudden death produce high mortality in turkeys. Rapid growth induced by high nutrient intake alone can cause severe lameness, bone defects, and deformity, as these problems are seen in animals that have not been selected for rapid growth: dogs, horses, pigs, ratites and wild birds kept in zoologic gardens. In meat-type poultry, growth-related disease can be reduced or eliminated by reducing feed intake without affecting final body weight. Rapid growth alone may not be the pathogenic mechanism that results in cardiovascular or musculoskeletal defects. Metabolic imbalance induced by high nutrient intake may cause some of the conditions. These metabolic problems might be corrected without reducing growth rate.     

Electrical activity in rat tail artery during asynchronous activation of postganglionic nerve terminals by ciguatoxin-1

1. The effects of ciguatoxin-1 (CTX-1) on the membrane potential of smooth muscle cells have been examined in rat proximal tail arteries isolated in vitro. 2. CTX-1 (> or = 10 pM) increased the frequency of spontaneous excitatory junction potentials (s.e.j.ps). At 100-400 pM, there was also a marked and maintained depolarization (19.7 +/- 1.4 mV, n = 14, at 400 pM). 3. In 20-400 pM CTX-1, perivascular stimuli evoked excitatory junction potentials (e.j.ps) which were prolonged in time course relative to control. 4. Although threshold and latency of the e.j.p. were not affected by CTX-1 (< or = 400 pM), propagated impulses were blocked at > or = 100 pM. 5. The spontaneous activity and the depolarization produced by CTX-1 were reduced in the presence of Ca2+ (0.1 mM)/Mg2+ (25 mM), omega-conotoxin (0.1 microM) or Cd2+ (50-100 microM). 6. All effects of CTX-1 were abolished by tetrodotoxin (0.3 microM). 7. Raised Ca2+ (6 mM) reduced the depolarization and spontaneous activity produced by CTX-1. 8. In 400 pM CTX-1, the membrane repolarized (17 +/- 3.2 mV, n = 4) following the addition of phentolamine (1 microM). S.e.j.ps and e.j.ps were selectively abolished by suramin (1 mM), and the membrane repolarized by 1.3 +/- 1.6 mV (n = 4). 9. We conclude that CTX-1 releases noradrenaline and ATP by initiating asynchronous discharge of postganglionic perivascular axons. In 100-400 pM CTX-1, the smooth muscle was depolarized to levels resembling those recorded in this artery during ongoing vasoconstrictor discharge in vivo.     

Changes in circadian rhythm of blood pressure in on-call pediatric residents

To provide an objective measure of the effects of on-call stress on the blood pressure (BP) of a group of pediatric residents, we used a SpaceLabs Ambulatory Blood Pressure Monitor (ABPM) to compare 37 pediatric residents' on- and off-call BPs. Residents wore the ABPM for 24 h (once on call and again off call) to assess systolic and diastolic BPs every 30 min during the day and hourly overnight. We found significantly higher MESOR (an acronym for midline estimating statistic of rhythm, which yields a mean value more representative of the true mean than an average of a series of measurements) BPs and BP loads (%BP readings > 135 mm Hg for systolic and/or 85 mm Hg diastolic) during the on-call period. Some residents became hypertensive on call, and the normal 24-h pattern of lower nighttime blood pressures was altered during this period. ABPM monitoring may prove useful in evaluating the effectiveness of interventions to reduce the stress of residency training.     

Inhibition of mammalian protoporphyrinogen oxidase by acifluorfen

We have studied the kinetics of the inhibition of mitochondrial protoporphyrinogen oxidase (PPO) from liver and placenta of 3 mammalian species by the diphenyl ether herbicide acifluorfen (AF). AF competitively inhibited PPO from human liver and placenta, mouse liver and pig placenta with respect to its substrate protoporphyrinogen. In contrast, mixed-type inhibition was shown for pig liver. The differing results shown in pig liver may point to structural differences in PPO derived from different species and tissues. We have also compared the effects of AF on the function of PPO in human lymphoblasts from normal subjects and those with variegate porphyria, an inherited disorder of PPO. Competitive inhibition was shown for both and there were no significant differences in the values of Ks or Ki.