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R A Hodgson

Publications and source records attributed to R A Hodgson.

11 recordsLinked to original sources
PubMed2005

Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species.

RATIONALE: Previous studies have demonstrated behaviors indicative of anxiolysis in rats pretreated with the nociceptin receptor (opioid receptor like-1, ORL-1) agonist, Ro64-6198. OBJECTIVES: The aim of this study was to examine the effects of Ro64-6198 in anxiety models across three species: rat, guinea pig, and mouse. In addition, the receptor specificity of Ro64-6198 was studied, using the ORL-1 receptor antagonist, J-113397, and ORL-1 receptor knockout (KO) mice. Finally, neurological studies examined potential side effects of Ro64-6198 in the rat and mouse. RESULTS: Ro64-6198 (3-10 mg/kg) increased punished responding in a rat conditioned lick suppression test similarly to chlordiazepoxide (6 mg/kg). This effect of Ro64-6198 was attenuated by J-113397 (10 mg/kg), but not the mu opioid antagonist, naltrexone (3 mg/kg). In addition, Ro64-6198 (1-3 mg/kg) reduced isolation-induced vocalizations in rat and guinea pig pups. Ro64-6198 (3 mg/kg) increased the proportion of punished responding in a mouse Geller-Seifter test in wild-type (WT) but not ORL-1 KO mice, whereas diazepam (1-5.6 mg/kg) was effective in both genotypes. In rats, Ro64-6198 reduced locomotor activity (LMA) and body temperature and impaired rotarod, beam walking, and fixed-ratio (FR) performance at doses of 10-30 mg/kg, i.e., three to ten times higher than an anxiolytic dose. In WT mice, Ro64-6198 (3-10 mg/kg) reduced LMA and rotarod performance, body temperature, and FR responding, but these same measures were unaffected in ORL-1 KO mice. Haloperidol (0.3-3 mg/kg) reduced these measures to a similar extent in both genotypes. These studies confirm the potent, ORL-1 receptor-mediated, anxiolytic-like effects of Ro64-6198, extending the findings across three species. Ro64-6198 has target-based side effects, although the magnitude of these effects varies across species.

Animals↗
PubMed2005

Training-induced and electrically induced potentiation in the neocortex.

Long-term potentiation (LTP) shares many properties with memory and is currently the most popular laboratory model of memory. Although it has not been proven that memory is based on an LTP-like mechanism, there is evidence that learning a motor skill can induce LTP-like effects. This evidence was obtained in a slice-preparation experiment, which precluded within-animal comparisons before and after training. In the present experiments, Long-Evans rats were unilaterally trained to acquire a forelimb reaching and grasping skill. Evoked potentials were found to be larger in motor cortex layer II/III in the trained, compared to the untrained, hemisphere in slice, acute, and chronic preparations. Consistent with previous research, the trained hemisphere was less amenable to subsequent LTP induction. Furthermore, the application of either LTP- or LTD-inducing stimulation during the training phase of the reaching task disrupted the acquisition of the skill, providing further evidence that memory may be based on an LTP mechanism.

Animals↗
PubMed1994

Probing the hammerhead ribozyme structure with ribonucleases.

Susceptibility to RNase digestion has been used to probe the conformation of the hammerhead ribozyme structure prepared from chemically synthesised RNAs. Less than about 1.5% of the total sample was digested to obtain a profile of RNase digestion sites. The observed digestion profiles confirmed the predicted base-paired secondary structure for the hammerhead. Digestion profiles of both cis and trans hammerhead structures were nearly identical which indicated that the structural interactions leading to self-cleavage were similar for both systems. Furthermore, the presence or absence of Mg2+ did not affect the RNase digestion profiles, thus indicating that Mg2+ did not modify the hammerhead structure significantly to induce self-cleavage. The base-paired stems I and II in the hammerhead structure were stable whereas stem III, which was susceptible to digestion, appeared to be an unstable region. The single strand domains separating the stems were susceptible to digestion with the exception of sites adjacent to guanosines; GL2.1 in the stem II loop and G12 in the conserved GAAAC sequence, which separates stems II and III. The absence of digestion at GL2.1 in the stem II hairpin loop of the hammerhead complex was maintained in uncomplexed ribozyme and in short oligonucleotides containing only the stem II hairpin region. In contrast, the G12 site became susceptible when the ribozyme was not complexed with its substrate. Overall the results are consistent with the role of Mg2+ in the hammerhead self-cleavage reaction being catalytic and not structural.

Base Composition↗
PubMed1989

Selective inhibition of photosystem II in spinach by tobacco mosaic virus: an effect of the viral coat protein.

Leaves of Spinacia oleracea inoculated with tobacco mosaic virus (TMV) strain PV230 develop mild chlorotic and mosaic symptoms of infection. Thylakoid membranes isolated from these infected leaves showed a reduced Fv/Fm ratio for chlorophyll fluorescence kinetics, at 25 degrees C. The photosystem II (PS II)-mediated electron-transport rate was inhibited 50%, whereas PS I activity was unaffected by virus infection. Protein analysis indicated that TMV coat protein was associated with thylakoids, in particular with the PS II fraction. The results demonstrate that TMV-infected S. oleracea shows inhibition of photosynthetic electron transport through PS II. We propose that the inhibition of photosynthetic activity results from the association of viral coat protein with the PS II complex.

Blotting, Western↗
PubMedDate not supplied

Characterization of the masked strain of tobacco mosaic virus: identification of the region responsible for symptom attenuation by analysis of an infectious cDNA clone.

A strain of tobacco mosaic virus (TMV) that produces mild (attenuated) symptoms on tobacco plants has been molecularly cloned to identify the region of the genome responsible for symptom attenuation. A full-length cDNA clone whose transcripts produce the parental disease phenotype on both systemic and hypersensitive host plants has been constructed. This infectious clone was sequenced, and 55 base changes relative to the published sequence of common TMV (strain U1) were identified. These changes resulted in 12 amino acid alterations in the open reading frames encoding the 126/183-kDa and 30-kDa movement proteins; two of these changes were determined not to be responsible for the attenuated phenotype. Exchange of restriction fragments between the infectious mild strain cDNA and an infectious U1 strain cDNA indicated that the determinants involved in symptom attenuation reside in the open reading frame encoding the 126/183-kDa proteins of TMV; these proteins are involved in viral replication.

Base Sequence↗