The Impact of Model Uncertainty on Benchmark Dose Estimation.

We study the popular benchmark dose (BMD) approach for estimation of low exposure levels in toxicological risk assessment, focusing on dose-response experiments with quantal data. In such settings, representations of the risk are traditionally based on a specified, parametric, dose-response model. It is a well-known concern, however, that uncertainty can exist in specification and selection of the model.

Drosophila Gr5a encodes a taste receptor tuned to trehalose.

Recent studies have suggested that Drosophila taste receptors are encoded by a family of G protein-coupled receptor genes comprising at least 56 members. One of these genes, Gr5a, has been shown by genetic analysis to be required by the fly for behavioral and sensory responses to a sugar, trehalose. Here, we show that Gr5a is expressed in neurons of taste sensilla located on the labellum and legs.

Ageing and the free radical theory.

The free radical theory proposes that ageing is the cumulative result of oxidative damage to the cells and tissues of the body that arises primarily as a result of aerobic metabolism. Several lines of evidence have been used to support this hypothesis including the claims that: (1) variation in species life span is correlated with metabolic rate and protective antioxidant activity; (2) enhanced expression of antioxidative enzymes in experimental animals can produce a significant increase in longevity; (3) cellular levels of free radical damage increases with age; and (4) reduced calorie intake leads to a decline in the production of reactive oxygen species and an increase in life span. The free radical theory may also be used to explain many of the structural features that develop with ageing including the lipid peroxidation of membranes, formation of age pigments, cross-linkage of proteins, DNA damage and decline of mitochondrial function.

Molecular characterisation of a putative Atlantic salmon (Salmo salar) odorant receptor.

The olfactory system of fish is extremely important as it is able to recognise and distinguish a vast array of odorous molecules that are involved in behaviours paramount to survival. This is achieved by the activation of a diverse multigene family of G-protein coupled receptors through odorous ligand binding. Using molecular techniques, the nucleotide sequence of the cDNA coding for an Atlantic salmon (Salmo salar) odorant receptor (ASOR1) has been determined.

Does prolactin mediate induced nest-building behaviour in pseudopregnant gilts treated with PGF2alpha?

Nest-building behaviour occurs 6-24 h before parturition in pigs (gestation=116 days). Pseudopregnancy in pigs (induced with oestradiol valerate injections) lasts 50-80 days. We have shown that prostaglandin F2alpha (PG) administration on day 47 of pseudopregnancy induces nest-building and changes to plasma prolactin, oxytocin, cortisol and progesterone similar to those seen before normal parturition.

Prostaglandin F2alpha-induced nest-building in pseudopregnant pigs. II. Space restriction stress does not influence secretion of oxytocin, prolactin, oestradiol or progesterone.

We have previously shown that prostaglandin F2alpha (PG) is capable of inducing nest-building behaviour in pseudopregnant gilts and established a protocol. This experiment examined which reproductive endocrine systems might mediate these behavioural responses, in the presence or absence of a space restriction stress. Pseudopregnancy was induced with 5 mg/day i.

Prostaglandin F2alpha-induced nest-building in pseudopregnant pigs. I. Effects of environment on behaviour and cortisol secretion.

Pigs may be susceptible to stress when they are strongly motivated to nest-build in a space-restricted environment. This study aimed to explore whether nest-building behaviour could be induced by prostaglandin F2alpha (PG) administration to pseudopregnant gilts and to determine whether induced behaviour and cortisol output differed between animals chronically placed in either farrowing crates or pens. Jugular vein catheters were placed on Day 39 of pseudopregnancy and blood samples collected daily from Day 40 to Day 48.

Circling behaviour induced by apomorphine after lesions of the habenula.

Apomorphine, 2 mg/kg (s.c.) produced significant contralateral turning in rats with unilateral radiofrequency lesions of the habenula nucleus over a test period of 60 min when tested at post-surgery days 3, 7, and 14.

Effect of delta 9-tetrahydrocannabinol on circling in rats induced by intranigral muscimol administration.

Unilateral injection of 25 ng of muscimol into the rat substantia nigra pars reticulata induced contralateral circling. Circling induced by 25 ng of muscimol was increased by simultaneous administration of 1 microgram of delta 9-tetrahydrocannabinol and abolished by 10 micrograms. Previous experiments have shown that delta 9-tetrahydrocannabinol enhances muscimol-induced catalepsy in the globus pallidus.

delta 9-Tetrahydrocannabinol and anandamide enhance the ability of muscimol to induce catalepsy in the globus pallidus of rats.

Doses of 3 or 30 micrograms of delta 9-tetrahydrocannabinol markedly increased the ability of 25 ng of muscimol to delay the descent of rats from a horizontal bar (descent latency) when these drugs were coadministered bilaterally into the globus pallidus. Intrapallidal injections of 30 micrograms of the putative endogenous cannabinoid, anandamide, also increased the effect of muscimol on descent latency. These data indicate that the production of catalepsy by cannabinoids may depend at least in part on an ability to enhance GABAergic transmission in the globus pallidus and support the hypothesis that anandamide is indeed an endogenous ligand for the cannabinoid receptor.

Enhancement by chlordiazepoxide of catalepsy induced in rats by intravenous or intrapallidal injections of enantiomeric cannabinoids.

The cataleptic response of rats to (-)-delta-9-tetrahydrocannabinol (delta-9-THC), measured using a bar test, was enhanced by subcutaneous pretreatment with chlordiazepoxide (10 mg/kg). Significant potentiation was observed when the cannabinoid was administered peripherally (0.1-1.

Intra-habenular injection of 6-hydroxydopamine produces impaired acquisition of DRL operant behavior.

The anatomical connections of the habenula complex indicate it provides a relay between limbic forebrain and midbrain. Somewhat paradoxically, consequences of nonspecific lesion of the habenula are ambiguous with little change in basic response evident within simple behavioral paradigms. However, the potential functional importance for this relay has more recently been indicated by the demonstration of deficits in the ability of lesioned animals to alter behavior appropriate to both internal and external stimuli in more demanding behavioral tasks.

A failure to support cross-sensitization between effects of apomorphine and lesions of the habenula nucleus.

An interchangeability between the effects of stress and psychostimulants has been reported. The possible common physiological effects of lesions of the habenula, stress and psychostimulant administration of activation of ascending dopamine systems suggested examination of a cross-sensitization between lesions of the habenula and psychostimulant administration. Lesions of the habenula were found to increase baseline activity but there were no significant changes in response to apomorphine in either various categories of stereotypy or locomotor response.

Changes in motor activities induced by microinjections of the selective dopamine agonists LY 171555, quinpirole hydrochloride, and SK&F 38393 into the habenula nucleus.

The effects on behaviour of microinjections into the habenula complex of selective agonists for dopamine D-1 (SK&F 38393) and D-2 (LY 171555) receptors were documented in a holeboard, open-field test. The D-2 agonist reduced grooming responses, locomotor activity and rearing behaviour. In contrast, the D-1 agonist increased rearing and locomotor activity but was without effect on grooming responses.