Candace J. Gibson

Release of Dopamine in the Nucleus Accumbens Caused By Stimulation of the Subiculum in Freely Moving Rats

Stimulation of the ventral subiculum of the hippocampus activates the hippocampal-accumbens pathway and increases locomotor activity. Dopaminergic terminals in the nucleus accumbens have also been implicated in initiation of locomotor activity, and the release of dopamine in the nucleus accumbens is critical for locomotor responses initiated from the subiculum to occur. We have demonstrated release of dopamine in the nucleus accumbens using in vivo microdialysis after stimulation of the ventral subiculum with NMDA. Extracellular dopamine level in the nucleus accumbens was significantly increased by 40% over baseline as a result of NMDA stimulation of the ventral subiculum. This stimulation also caused more than a 40-fold increase in horizontal activity and total distance covered by the rats. Injection of saline into the subiculum caused neither a change in the dopamine level nor an increase in animals activity. The dynamics of the measured changes in dopamine overflow correlated with the time course of locomotor changes. The results demonstrate that stimulation of the ventral subiculum causes release of dopamine in the nucleus accumbens which parallels the increase in locomotor activity.

The effects of propofol in the area postrema of rats.

Propofol has an antiemetic effect that may be mediated by &ggr;-aminobutyric acid (GABA) influences on the serotonin system, the mechanism of which is not known. We used three techniques, immunohistochemistry, High Performance Liquid Chromatography, and electrophysiology, to define propofol’s effects on the rat’s brainstem. Paired male Wistar rats received propofol, 20 mg/kg/hr, or Intralipid® for 6 h. The brains were then subjected to immunohistochemical analysis of serotonin. In a separate experiment after a propofol or Intralipid® infusion, cerebrospinal fluid (CSF) was extracted from the fourth ventricle and analyzed for the amount of serotonin and 5-hydroxyindoleacetic acid. Electrophysiological neuronal recordings were made in the area postrema (AP) in response to propofol with and without a GABA or serotonin antagonist. Results showed that immunohistochemical staining for serotonin in the propofol rats was significantly increased (28 ± 12%) in the dorsal raphe and decreased in the AP (17 ± 6%) compared with control. There were no significant changes in the isoflurane-anesthetized animals. Both serotonin and 5-hydroxyindoleacetic acid in the CSF of the fourth ventricle at the level of the AP were significantly reduced by 63% and 36%, respectively. Both propofol and pentobarbital injections reduce AP neuronal activity, but only the propofol response was blocked by bicuculline, a GABA antagonist. We conclude that the reduced levels of serotonin in the AP and the CSF may explain the antiemetic property of propofol. Propofol may also directly act on AP neurons via a GABAA receptor to reduce their activity.

Changes in plasma catecholamine levels after insula damage in experimental stroke

The effect of permanent occlusion of the left middle cerebral artery (MCA) on plasma catecholamine levels was investigated in chloralose-anesthetized cats. Two-5 h after occlusion of the MCA the plasma levels of norepinephrine, epinephrine and dopamine were significantly elevated (33%, 44% and 28%, respectively) compared to preocclusion levels only in animals in which the cerebral infarction involved the insular cortex. No significant changes were observed in plasma catecholamine levels in animals in which either the infarction did not involve the insula or in sham-stroked animals. These data suggest that withdrawal of inhibitory inputs from the insula on central cardiovascular regulating centers after stroke results in an increase in the activity of the sympathoadrenal system.

Inhibition of MAO B, but not MAO A, blocks DSP-4 toxicity on central NE neurons.

The neurotoxin, DSP-4, (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) specifically and significantly reduces norepinephrine (NE) and its metabolite, 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), in cortical, hippocampal and cerebellar brain regions. Pretreatment with the selective monoamine oxidase (MAO) B inhibitor, deprenyl, and the non-specific MAO inhibitor, pargyline, effectively blocked NE depletion. Pretreatment with the selective MAO A inhibitor, clorgyline, had no effect on central NE DSP-4 toxicity. Thus formation of a toxic metabolite by the action of MAO B may be involved in DSP-4 induced neural damage.

Tyrosine for depression.

The catecholamine hypothesis of affective disorders postulates that depression reflects inadequate norepinephrine activity at unspecified brain centers that regulate mood. In light of experimental data showing that the oral administration of tyrosine, precursor of the catecholamine series of neurotransmitters, can increase brain norepinephrine concentrations and activity, we have conducted preliminary trials of tyrosine in depressed outpatients. Initial results are encouraging, and we are now conducting a double-blind, parallel-group trial comparing tyrosine to the tricyclic antidepressant imipramine and to placebo in non-bipolar outpatients with major depression.

The development and assessment of an online microscopic anatomy laboratory course.

Increasing enrollment in post‐secondary institutions across North America, along with an increase in popularity of and demand for distance education is pressuring institutions to offer a greater number and variety of courses online. A fully online laboratory course in microscopic anatomy (histology) which can be taught simultaneously with a face‐to‐face (F2F) version of the same course has been developed. This full year course was offered in the Fall/Winter (FW) terms in both F2F and online formats. To ensure that the online course was of the same quality as the F2F format, a number of performance indicators were evaluated. The same course, offered exclusively online during the summer with a compressed time frame, was also evaluated. Senior undergraduate students self‐selected which version of the course they would enroll in. Course assessment outcomes were compared while incoming grades were used as a predictor for course performance. There were no significant differences between the incoming grades for the F2F FW and Online FW courses; similarly, there were no significant differences between outcomes for these formats. There were significant differences between the incoming grades of the F2F FW and Summer Online students. However, there were no significant differences among any of the outcomes for any of the formats offered. Incoming grades were strong, significant predictors of course performance for both formats. These results indicate that an online laboratory course in microscopic anatomy is an effective format for delivering histology course content, therefore giving students greater options for course selections. Anat Sci Educ 6: 246–256.

ENDANGERED SPECIES : SCIENCE WRITERS IN THE CANADIAN DAILY PRESS

The last comprehensive study of Canadian science journalists and science reporting was done over 20 years ago (Dubas and Martel 1973). A more recent content analysis of seven major Canadian dailies found most science stories are “hard” news in style and originate from wire sources (Einsiedel 1992). This 1994 survey of 105 of Canadas daily English-language newspapers and their commitment to science journalism revealed a general weakening and dilution of reporter allocation. Over 50 percent of Canadian dailies did not allocate a science reporter. Only 18 full-time science reporters were identified. A follow-up of 45 journalists covering science at least half-time revealed most covered science policy. The vast majority had no science training. Time problems and competing demands hindered professional development. Confirming suggestions of previous literature, this study also indicates the Canadian daily newspaper structure is not supportive of the style of reportage required for quality science writing, nor of the development of such writers.

Zinc supplementation decreases hepatic copper accumulation in LEC rat: a model of Wilson's disease.

The effect of dietary zinc (Zn) supplementation on copper (Cu)-induced liver damage was investigated in Long-Evans Cinnamon rats (LEC), a model for Wilsons disease (WD). Four-week-old LEC (N=64) and control Long-Evans (LE) (N=32) female rats were divided into two groups; one group was fed with a Zn-supplemented diet (group I) and the other was given a normal rodent diet (group II). LEC rats were killed at 6, 8, 10, 12, 18, and 20 wk of age; the LE control rats were killed at 6, 12, 18, and 20 wk of age. Cu concentration in the liver was reduced in LEC rats fed the Zn-supplemented diet compared with LEC rats on the normal diet between 6 and 18 wk of age. Metallothionein (MT) concentration in the livers of LEC rats in group I increased between 12 and 20 wk of age, whereas hepatic MT concentration in LEC rats from group II decreased after 12 wk. Hepatocyte apoptosis, as determined by TUNEL, was reduced in Zn-supplemented LEC rats at all ages. Cholangiocellular carcinoma was observed only in LEC rats in group II at wk 20. These results suggest that Zn supplementation can reduce hepatic Cu concentration and delay the onset of clinical and pathological changes of Cu toxicity in LEC rats. Although the actual mechanism of protection is unknown, it could be explained by sequestration of dietary Cu by intestinal MT, induced by high dietary Zn content.

Pharmacological characterization of grooming induced by a selective NK-1 tachykinin receptor agonist

Bilateral intranigral administration of the selective NK-1 tachykinin receptor agonist [AcArg6, Sar9, Met(O2)11]SP6-11 (0-1 nmol total bilateral dose) selectively induced grooming in rats. This response was blocked by concurrent intranigral administration of the NK-1 tachykinin receptor antagonist RP 67580 (2 nmol), but not by NK-2 (L-659,877) or NK-3 ([Trp7, beta-Ala8]NKA4-10) antagonists. Pretreatment with systemic opioid (naloxone 1.5 mg/kg) and D1 dopamine (SCH 23390 100 micrograms/kg) receptor antagonists also attenuated tachykinin-induced grooming, which was unaffected by D2 dopamine (sulpiride 30 mg/kg) or 5-HT2A+C (ritanserin 2 mg/kg) antagonists. Grooming induced by intranigral [AcArg6, Sar9, Met(O2)11]SP6-11 was also attenuated by bilateral 6-hydroxydopamine lesions of the substantia nigra. These findings indicate that grooming induced by intranigral tachykinins reflects activation of NK-1 receptors and is dependent upon endogenous dopamine and consequent selective stimulation of D1 dopamine receptors.

Chromogranin A inhibits retinal dopamine release

Chromogranin A (CGA), a peripherally active prohormone, is a soluble component in the secretory granules of many endocrine tissues and is cosecreted with their peptide or amine hormones. Using an antibody prepared against purified rat adrenal CGA, immunostaining was localized to the inner and outer plexiform layers of the rat retina and to selected ganglion cells. Exogenous CGA (purified from human adrenals) when applied to perfused rat retina potently inhibited the potassium-induced release of endogenous dopamine (DA). This action was dose-dependent, with an IC50 of 3 nM; at 100 nM CGA retinal DA release was completely abolished.