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The aim of this thesis is to determine whether having an ability to choose otherwise aids our understanding of the kind of balanced autonomy that is required in order to claim that people should be held responsible for their actions. By looking to the theories of three historical philosophers (Friedrich Nietzsche, Martin Heidegger, Jean Paul Sartre), I find evidence that suggests having an ability to choose otherwise should not be the ground on which we base responsibility for an agent’s actions; actions involve ‘choosing one’s self’ and there is a relationship one has to one’s self which is often overlooked. My investigation reveals evidence that existential authenticity is an inherent quality of autonomy and that the ‘genuine self’ which grounds an agent’s actions ought to be viewed as a ‘dependence’ rather than a ‘cause’. My investigation also reveals a concept of a ‘genuine self’ as distinct from the concept of a narratively structured ‘ego’; the self and the ego appear to be distinct entities which are existentially interdependent. This thesis raises questions which should be addressed in future investigations. First, how is, and how should responsibility be related to the dependences from which actions arise and second, is the objective world best understood as causally structured, in accordance with the doctrine of determinism, or rather, should we seek an understanding of the objective world as dependently structured. / Thesis / Master of Philosophy (MA) / Is having an ability to choose otherwise the best ground on which to hold persons responsible for their actions? This thesis considers the works of Friedrich Nietzsche, Martin Heidegger and Jean-Paul Sartre, which reveal some evidence that persons should not be held responsible for their actions on the basis of being able to choose otherwise. I argue that authenticity is an inherent feature of autonomy which involves the relationship one has to one’s self and ‘choosing one’s self’; and that there is a distinction to be made between the ‘ego’ and the ‘self’. Further, I advance an argument that actions are dependent on a ‘self’, but that the ‘self’ is not a cause of action. This thesis raises questions to be addressed in future investigations regarding the connection between responsibility and dependence as well as whether the world is best understood as dependently structured rather than causally structured.

Background: Planarians have mammalian-like neurotransmitter systems and have been established as a novel in vivo model for neuropharmacology. In previous research, planarians exposed to the cannabinoid receptor (CB-R) agonist WIN 55,212-2 (10 μmol/L) for 1 h displayed a significant (p < 0.05) decrease in spontaneous locomotor velocity (pLMV) when subsequently tested in drug-free, but not in drug-containing, water. This demonstrated abstinence-induced withdrawal from a CB-R agonist as a manifestation of the development of physical dependence. Purpose: The purpose of the present study was to extend previous work and to further establish a cannabinoid behavioral model with planarians. Specifically, the goals included (i) confirm the work with WIN 55,212-2 and extend to a second agonist (ii) interfere with agonist-induced physical dependence using several CB-R antagonists, (ii) demonstrate antagonist-induced precipitated withdrawal behavior, and (iii) try to induce withdrawal behavior from CB-R agonists using UV light. Methods: Two CB agonists (WIN 55,212-2 and JWH251) and four CB antagonists (AM251, AM281, SLV319 and SR144528) were used. Planarians were placed individually in CB-R agonist or agonist + antagonist mixtures for 20 and 30 min of exposure (with or without UV radiation), and withdrawal was quantified by measuring pLMV in drug-free vs drug-containing water (with or without UV light irradiation). Results: (i) Four different CB1-R antagonists (AM251, AM281, SLV319 and SR144528) dose-relatedly blocked development of physical dependence induced by two different CB-R agonists (WIN 55,212-2 and JWH251). (ii) None of the same four antagonists (AM251, AM281, SLV319 and SR144528) precipitated withdrawal. (iii) Short wavelength (254 nm), but not long wavelength (366 nm), UV light attenuated abstinence-induced withdrawal from WIN 55,212-2, while short wavelength UV light induced moderate withdrawal behavior. Conclusions: The results confirm the use of a planarian model as a simple yet robust way to study development of physical dependence to cannabinoid agonists. The model is more rapid and sensitive than the usual rodent models. The effect of UV irradiation adds to the supposition that the results are receptor-related. The results also give rise to the surprising suggestion, within the limitations of the methodology, that development of cannabinoid physical dependence and antagonist-induced precipitated withdrawal might be separable phenomena in planarians. / Pharmaceutical Sciences