Aquatic biosurvey of the Lovell River on UNH land

We assessed the physical, chemical and biological conditions at two sites along the Lovell River on University of New Hampshire (UNH) -owned conservation land. The discharge was 4.4 m3 s-1 at Site 1 and 5.7 m3 s -1 downstream at Site 2. Canopy coverage ranged from 8-25%. Canopy was dominated by Eastern Hemlock (79-84%). Much of the stream was strewn with large boulders and the substrate consisted of rocks of highly variable sizes ( 3-549 cm dia.). Specific conductivity (22.1-23.3 µS), pH (6.4) and temperature (7.9-8.3 °C) varied little between sites. Macro-invertebrate bio-indices indicated either excellent water quality with no apparent organic pollution (3.0/10) or good water quality with possible slight organic pollution (4.4/10)

Epistasis among Presynaptic Serotonergic System Components

Epistatic interactions among regulatory components of the serotonin (5-HT) neurotransmitter system may be an important aspect of 5-HT function. Because 5-HT dysregulation is associated with several common psychiatric disorders, the potential for epistasis among genetic variants in the 5-HT transporter (SERT), 5-HT 1B terminal autoreceptor and the 5-HT 1A somatodendritic autoreceptor should be examined. In this study, output from a dynamic minimal model of 5-HT function was compared to empirical results in the literature. Parameters representing extracellular 5-HT clearance rates (SERT), 5-HT release levels (5-HT 1B ) and inhibitory thresholds (the amount of extracellular 5-HT above which cell firing is inhibited, an indication of 5-HT 1A autoreceptor sensitivity) were varied to simulate genetic deletion (i.e. knockout) of each component singly, and in combination. Simulated knockout effects on extracellular 5-HT level and presynaptic neural firing rates were in the same direction and of similar relative magnitude as studies in the literature. Epistasis among presynaptic components appears to be important in the 5-HT system’s regulation of extracellular 5-HT levels, but not of firing rates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44113/1/10519_2004_Article_1019.pd

Regulation of extracellular concentrations of serotonin by 5-HT(1A) and 5-HT(1B) autoreceptors in mice

The somatodendritic 5-HT1A autoreceptor and the terminal 5-HT1B autoreceptor are both able to alter extracellular levels of 5-HT by regulating its release from 5-HT nerve terminals. The studies in this thesis developed a novel application for the technique of in vivo microdialysis in order to investigate the fundamental differences between these two autoreceptors. The first set of studies examined the pharmacological differences between the 5-HT1A and 5-HT1B autoreceptors in mice. These studies characterized the novel 5-HT1A receptor agonist R-8-OH-PIPAT and the novel 5-HT1B receptor agonist CP 94,253. It was determined that both the 5-HT1A and 5-HT1B autoreceptors are able to regulate 5-HT release in the striatum of wild-type (129/SVEM) mice but through distinct pharmacological means. In addition, these initial studies determined that in vivo microdialysis is a viable technique in mice. The regional specificity for autoreceptor regulation of 5-HT release was then explored. These studies utilized 5-HT1A or 5-HT1B receptor knockout mice. It was determined that systemic administration of fluoxetine elicited a significantly greater increase in extracellular 5-HT in the striatum, a dorsal raphe innervated brain region, of 5-HT1A receptor knockout mice as compared to wild-type. A significantly greater increase in extracellular 5-HT in the ventral hippocampus, a median raphe innervated brain region, of the 5-HT1B receptor knockout mice as compared to wild-type was also observed. This indicated a distinct regional hierarchy for autoreceptor regulation of 5-HT release. These effects were not due to developmental alterations in the receptor knockout mice because parallel studies in wild-type mice using receptor antagonists produced the same pattern of effects. In the final set of studies, the physiological reorganization that occurs in response to genetic deletion of a 5-HT autoreceptor was determined. It was discovered that 5-HT1B receptors in the striatum of 5-HT 1A receptor knockout Mice bad an increased responsiveness, whereas the responsiveness of the 5-HT1A receptors measured in the ventral hippocampus, of the 5-HT1B receptor knockout mice was decreased. These experiments determined that the 5-HT1A and 5-HT 1B autoreceptors have distinct pharmacological means and topographical hierarchy for regulating 5-HT release, and genetic deletion of each of these autoreceptors results in distinct physiological reorganization

Regulation of extracellular concentrations of serotonin by 5-HT(1A) and 5-HT(1B) autoreceptors in mice

The somatodendritic 5-HT1A autoreceptor and the terminal 5-HT1B autoreceptor are both able to alter extracellular levels of 5-HT by regulating its release from 5-HT nerve terminals. The studies in this thesis developed a novel application for the technique of in vivo microdialysis in order to investigate the fundamental differences between these two autoreceptors. The first set of studies examined the pharmacological differences between the 5-HT1A and 5-HT1B autoreceptors in mice. These studies characterized the novel 5-HT1A receptor agonist R-8-OH-PIPAT and the novel 5-HT1B receptor agonist CP 94,253. It was determined that both the 5-HT1A and 5-HT1B autoreceptors are able to regulate 5-HT release in the striatum of wild-type (129/SVEM) mice but through distinct pharmacological means. In addition, these initial studies determined that in vivo microdialysis is a viable technique in mice. The regional specificity for autoreceptor regulation of 5-HT release was then explored. These studies utilized 5-HT1A or 5-HT1B receptor knockout mice. It was determined that systemic administration of fluoxetine elicited a significantly greater increase in extracellular 5-HT in the striatum, a dorsal raphe innervated brain region, of 5-HT1A receptor knockout mice as compared to wild-type. A significantly greater increase in extracellular 5-HT in the ventral hippocampus, a median raphe innervated brain region, of the 5-HT1B receptor knockout mice as compared to wild-type was also observed. This indicated a distinct regional hierarchy for autoreceptor regulation of 5-HT release. These effects were not due to developmental alterations in the receptor knockout mice because parallel studies in wild-type mice using receptor antagonists produced the same pattern of effects. In the final set of studies, the physiological reorganization that occurs in response to genetic deletion of a 5-HT autoreceptor was determined. It was discovered that 5-HT1B receptors in the striatum of 5-HT 1A receptor knockout Mice bad an increased responsiveness, whereas the responsiveness of the 5-HT1A receptors measured in the ventral hippocampus, of the 5-HT1B receptor knockout mice was decreased. These experiments determined that the 5-HT1A and 5-HT 1B autoreceptors have distinct pharmacological means and topographical hierarchy for regulating 5-HT release, and genetic deletion of each of these autoreceptors results in distinct physiological reorganization

Regional patterns of compensation following genetic deletion of either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) receptor in the mouse.

ABSTRACT Plasticity in serotonergic transmission in serotonin or 5-hydroxytryptamine (5-HT) receptor mutants was examined by measuring the regulation of extracellular 5-HT levels in the striatum and ventral hippocampus of 5-HT 1A and 5-HT 1B receptor knockout mice using in vivo microdialysis. The efficacy of genetic deletion was verified by showing blunted regulation of extracellular 5-HT with selective 5-HT receptor agonists. 5-HT 1A receptor knockout mice failed to demonstrate reduction of extracellular 5-HT in response to systemic administration of the 5-HT 1A receptor agonist R-8-hydroxydipropylaminotetralin (R-8-OH-DPAT) and 5-HT 1B receptor knockout mice failed to demonstrate reduction of extracellular 5-HT in response to systemic administration of the 5-HT 1B receptor agonist CP 94,253. Plasticity also developed to deletion of the complementary autoreceptor. 5-HT 1A receptor knockout mice demonstrated a significantly greater response to CP 94,253 in the striatum, but not the ventral hippocampus, suggesting the development of enhanced sensitivity of striatal 5-HT 1B receptors. In 5-HT 1B receptor knockout mice, R-8-OH-DPAT evoked a significantly diminished response in the ventral hippocampus, but not the striatum, suggesting the potential desensitization of 5-HT 1A receptors in the median raphe nucleus. The pattern of regional compensations between somatodendritic and terminal autoreceptors was confirmed by pharmacological challenges using the selective serotonin reuptake inhibitor fluoxetine combined with either a 5-HT 1A (WAY 100635) or a 5-HT 1B/1D (GR 127935) receptor antagonist. The regional pattern of compensation may be determined by the preferential role of 5-HT 1A or 5-HT 1B receptors in regulating 5-HT release. Taken together, these results demonstrate the development of regional plasticity between complementary somatodendritic and terminal autoreceptors after the genetic deletion of 5-HT 1A or 5-HT 1B receptors. Two types of serotonin or 5-hydroxytryptamine (5-HT) autoreceptors provide critical regulation of 5-HT release in the rat brain by supplying mechanisms for presynaptic inhibitory feedback. The 5-HT 1A autoreceptors are located in the somatodendritic neuronal region, at the site of the serotonergic cell bodies in the dorsal (DR) or median (MR) raphe nucleus, and regulate the release of 5-HT by modulating neurotransmitter synthesis, terminal release, and cell discharge rate The ability of autoreceptors to regulate extracellular levels of 5-HT during release has made them the focus of much interest. 5-HT autoreceptors are desensitized by the chronic administration of antidepressant drugs and this may account for the delay in appearance of therapeutic effect