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The following is a curated selection of biographical materials, poetic observations, amateur scientific and psychological inquiries mixed with a dash of extraterrestrial, spiritual, or otherworldly unknowing and finished off with philosophical meanderings that toe the line with anti-anxiety propaganda. A series of small narratives and inquiries about material usage and imagery within my sculptures act not as a guide but as an organization of information, an index of indexes of seemingly disparate materials grouped to try and express a whole. Exploring the delicate relationships between frequency, temperature, brain chemistry, consciousness, and climate poetically, this thesis attempts to question and reframe ideas of freedom, individualism, and linearity in time and perspective.

Over 47 percent of Americans take at least one prescription drug per month and of these pharmaceuticals, antidepressants are the third most prescribed drug. Their widespread and prolonged use coupled with incomplete removal during wastewater treatment processes has made them one of the most commonly detected pharmaceuticals in the aquatic environment. Antidepressants are intended to modify human behavior by altering brain chemistry and the neurotransmitter receptor targets of these chemicals are highly conserved in many vertebrate species; thus, aquatic organisms may be at risk. Previous research in our lab has shown that exposure of hybrid striped bass (HSB) (Morone saxatilis x. M. chrysops) to serotonin targeting antidepressants causes decreased in brain serotonin concentrations that correlate with significant changes in time to capture prey. The goal of this dissertation was to gain a better understanding of how antidepressants alter brain chemistry and predatory behavior in the hybrid striped bass, and to utilize the information to develop a preliminary model to predict the effects of antidepressants on fish brain chemistry and behavior. Hybrid striped bass were exposed to bupropion, a norepinephrine and dopamine reuptake inhibitor antidepressant, to understand if alteration of the dopaminergic neurotransmitter concentrations in the HSB would alter a predator’s ability to capture prey. HSB were exposed to bupropion in a static system for 6 days, followed by a 6 day recovery period. Bupropion altered the concentration of dopamine and many of the dopaminergic neurotransmitter metabolite concentrations in the HSB brains on day 3 of the exposure, but it did not alter the HSB time to capture prey. The lack of effect on time to capture prey suggests that alteration of dopaminergic neurotransmitter concentrations in the HSB brain does not alter a predator’s ability to capture prey and led to focusing of future work on serotonin targeting antidepressants, such as the selective serotonin reuptake inhibitor (SSRI) class. The target of SSRI antidepressants is the serotonin reuptake transporter (SERT). The SERT transporter has been identified in a few fish species, but not the hybrid striped bass. I utilized recently sequenced striped bass and white bass transcriptomes as well as conserved sequences from aligned serotonin reuptake transporters of other vertebrate species to design primers for cloning. I was able to sequence roughly 80% of the SERT, compared to the striped bass sequence, and found that it had 72% identity to the human SERT. The functional domains identified in the human SERT were highly conserved with the amino acid residues in the hybrid striped bass. The binding affinity of SSRI antidepressants were quantified for the SERT in a HSB brain homogenate using competitive radioligand binding assays with [3H] citalopram, a tritium labeled SSRI. In general, the HSB antidepressant binding affinities were less potent than affinities observed for the human SERT. These results confirmed that the SERT is conserved and present in the HSB, and that antidepressants are binding to the SERT in the HSB brain. The bioavailability of two serotonin targeting antidepressants, fluoxetine and venlafaxine, was quantified by exposing HSB to each drug and quantifying antidepressant concentrations in HSB plasma and brains. Fluoxetine and venlafaxine brain concentrations strongly correlated with decreases in brain serotonin concentrations and time to capture prey, providing internal antidepressant concentrations that correspond to adverse effects on HSB brain serotonin and predatory behavior. Antidepressants are entering the aquatic environment in complex mixtures. In order to gain a better understanding of the effects of SSRI antidepressant mixtures on fish brain chemistry and behavior, HSB were exposed to a mixture of sertraline, citalopram, and fluoxetine for 6 days, followed by a 6 day recovery period. The antidepressants were detected in the brains of the HSB throughout the recovery period, and significant changes in all treatments were observed on day 12 of the experiment, which correlated with significant increases in time to capture prey. Further, greater than additive changes in brain serotonin were observed in the experiment. Overall, the results of this dissertation indicate that SSRI antidepressants are binding to the SERT in the HSB brain and causing adverse effects on brain serotonin and time to capture prey. I have quantified the partitioning of antidepressants from aqueous exposures, to plasma concentrations, to ultimately reaching the brain and exerting effects on brain serotonin. These drugs can remain in the brain of the HSB even after being in a clean system for 6 days, and can continue to exert greater than additive effects on brain serotonin and alter predatory behavior. The work has furthered our understanding on how antidepressants in the environment alter hybrid striped bass brain serotonin and predatory behavior.

Advances in Analytical Chemistry have led to the detection of low concentrations of pharmaceuticals and personal care products (PPCPs) in wastewater treatment plant effluents as well as their receiving waters. Antidepressants are routinely found among these contaminants, but have been shown to be relatively non-toxic at environmentally measured concentrations using traditional toxicity testing techniques. The neurochemical mode of action of antidepressants warrants investigation of the effects these chemicals may have on fish behavior due to the highly conserved nature of neurotransmitter transporter targets. Using a predator prey bioassay designed in our laboratory, previous studies has shown that the antidepressant fluoxetine (Prozac®) causes significant effects on hybrid striped bass ability to capture prey. Increased time to capture prey was also correlated with decreasing brain serotonin concentrations. The goal of my dissertation was to expand our knowledge on the effects of antidepressant contaminants on the predation behavior and brain chemistry of hybrid striped bass (bass). Bass were exposed to the antidepressant fluoxetine for 27 days to determine if exposure duration has an effect on the behavioral toxicity of this chemical. We found that fluoxetine was only toxic at the same threshold found in our previous six day exposure studies and that longer term exposures did not decrease effective concentrations. Bass were exposed to the antidepressant venlafaxine (Effexor®) for six days followed by a six day recovery period at concentrations of 50, 250, and 500 µg/L. Concentrations of 250 and 500 µg/L had a significant effect on the time to capture prey 1-3 by day six while the 50 µg/L treatment only had a significant effect on bass ability to capture prey 3. Bass were able to recover their ability to capture prey 1 and 2 but time to capture prey 3 remained elevated for all treatments after six days of depuration. Venlafaxine had a significant effect on brain serotonin concentrations, which decreased in a dose dependent manner on day three and reached a basal level for all treatments on day six. Results indicated that venlafaxine may affect appetite at low concentrations and locomotor activity at high concentrations. Using the concentrations that caused a 15% decrease in brain serotonin concentrations from our previous studies with individual exposures to fluoxetine and venlafaxine, a simple mixture exposure was performed with 1 toxic unit representing 15 µg/L of fluoxetine and 25 µg/L of venlafaxine. Concentrations of 1, 2, and 4 toxic units caused a significant increase in the time to capture prey 2 and 3 by day six. Brain serotonin concentrations reached a basal level for all mixture treatments by day three and remained decreased through day six. There was a strong exponential correlation between brain serotonin concentrations and time to capture prey 1 and 2 on day six. When comparing mixture results to the results of individual antidepressant exposures, the data indicated low concentration mixtures may act in an additive manner causing increased time to capture prey and decreased brain serotonin concentrations at half the respective concentrations of each of the individual compounds. But this effect did not increase for the higher mixture exposure concentrations. Overall, the results of my dissertation indicate that antidepressants, even when present in low concentration mixtures, may present a significant risk aquatic organism behavior. Because effects on behavior can impact the fitness of an organism both directly and indirectly, it has implications for the population level. Though behavior is not typically used as an endpoint for risk assessment of aquatic contaminants, the behavioral mode of action of antidepressants and results of this study may warrant their inclusion.

In short, the writing process is affected by brain chemistry. Hormonal shifts, manic and depressive brain states, and even one’s level of endorphins produce good or bad moods that affect brain chemistry, which in turn influences the creative impulse. Altering brain states can serve to inspire prolific writing as well as to close a writer down—blocking her ability to communicate her ideas, frozen in panic. For example, a manic, or “high,” elevates one’s ability to write while the counterbalancing “low” or depressed brain tends to deflate the enthusiasm a smooth flow of ideas requires. The creative impulse is useful in motivating a writer. It is a valuable channeling of energy that, when neglected, may produce anxiety and psychological, even physical detriments. The physical brain helps one see the organic nature of creativity and, in doing so, consider ways to prepare the body to write.

The neurophysiological basis of cognition changes with age is relatively unexplained, with most studies reporting weak relationships between cognition and measures of brain function, such as event related potentials, brain size and cerebral blood flow. Proton magnetic resonance spectroscopy (1H-MRS) is an in vivo method used to detect metabolites within the brain that are relevant to certain brain processes. Recent studies have shown that these metabolites, in particular N-acetyl aspartate (NAA), which is associated with neuronal viability, correlate with performance on neuropsychological tests or other measures of cognitive function in patients with a variety of cognitive disorders associated with ageing and in normal ageing subjects. We have studied the relationship between metabolites and cognitive function in elderly patients 3 months and 3 years after a stroke or transient ischemic attack (TIA) and in an ageing comparison group. Metabolites were no different between stroke/TIA patients and elderly controls, however, there were significant metabolite differences between stroke/TIA patients with cognitive impairment (Vascular Cognitive Impairment and Vascular Dementia) and those without. Frontal measures of NAA and NAA/Cr predicted cognitive decline over 12 months and 3 years in stroke/TIA patients and elderly controls, and these measures were superior predictors than structural MRI measures. Longitudinal stability of metabolites in ageing over 3 years was associated with stability of cognitive function. The results indicate that 1H-MRS is a useful tool in differentiating stroke/TIA patients with and without cognitive impairment, with possibly superior predictive ability than structural MRI for assessing future cognitive decline. The changes in 1H-MRS that occur with ageing and cognitive decline have implications for the neurophysiological mechanisms and processes that are occurring in the brain, as well as application to clinical diagnosis, the early detection of pathology and the examination of longitudinal change.

This study presented evidence for the existence of a membrane-bound, sodium-activated ATPase which does not require potassium ions for its activity. Furthermore, the data suggest the presence of a soluble factor which activates this enzyme and may play a regulatory role in sodium transport.

From the standpoint of physiologists, emphasis has been placed on viewing the chemical nature of the membrane as an operational barrier to the free diffusion of ions. This tends to explain the fact that the ionic composition of the cytoplasm of the animal cell differs from its external fluid environment.It is well know that where sodium is the principal cation of the extracellular fluid, potassium has such a role inside the cell. Since there appears to be differential distribution of these ions across the cell membrane, this infers a concentration gradient of these ions. This differential distribution is important for certain life processes, for example, the propagation of nervous impulses mainly is dependent on the changes in concentration of sodium and potassium ions on both sides of the axonal membrane. Much effort has been put into elucidating the mechanism which cells maintain and change such concentration gradients. The enzyme system investigated in this study, namely, the sodium-activated adenosine triphosphatase, might be involved in maintaining this ionic gradient.