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Sex Differences In Mood And Anxiety-Related Outcomes In Response To Adolescent Nicotine Exposure, Tsun Hay Jason Ng

Electronic Thesis and Dissertation Repository

Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine …

Recovery From Social Isolation In Drosophila: The Role Of Dopamine And The Autism-Related Gene Nlg3., Ryley T. Yost

Electronic Thesis and Dissertation Repository

Within a group, individuals establish their preferred distance from each other, or social space, a form of social behaviour. The resulting distance depends on the exchange of social cues from others that needs to be perceived and integrated within the organism’s neural circuitry. In humans, social spacing can be impaired in neuropsychiatric disorders such as autism and schizophrenia. When organisms are subject to social isolation, profound changes in social behaviour are observed in a variety of species from insects to mammals, including social space. However, the genetic and molecular mechanisms modulating a behavioural response to isolation and possible recovery remain …

Dopaminergic Modulation Of A Fast Visuomotor Pathway In Parkinson's Disease, Madeline C. Gilchrist

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is associated with reduced dopaminergic (DA) input to the dorsal striatum (DS). This study investigated the role of DA in modulating automatic, stimulus-driven reactions by assessing contextual control of stimulus-locked responses (SLRs) in 10 PD patients off and on DA medication. The SLR is the rapid recruitment of limb muscles that drives the arm towards suddenly appearing stimuli. Participants reached away from (anti-reach) or towards (pro-reach) a target on a screen, depending on instruction appearing 500 or 1000ms before target appearance. Modulation of SLRs was assessed by comparing SLR magnitude on anti- and pro-reach trials using surface …

Early Experience And The Functional Calibration Of The Stress-Response Systems, Niki Hosseini-Kamkar

Electronic Thesis and Dissertation Repository

Individuals exposed to adversities in childhood are at a greater risk of developing various diseases as adults, including cardiovascular disease and cancer (Felitti et al. 1998). These findings have sparked an interest in examining biological mechanisms that might explain the link between exposure to adversity and disease. To date, evidence has linked adversity to the function of the hypothalamic-pituitary-adrenal (HPA) axis. More recently, adversity has been associated with the function of the mesolimbic dopamine pathway as well.

This thesis uses a variety of techniques to explore the association between adversity and the function of the HPA axis and mesolimbic dopamine …

Cholinergic Modulation Of Behaviour, Ornela Kljakic

Electronic Thesis and Dissertation Repository

The cholinergic system is one of the most influential and essential signalling systems in the body. In the brain, cholinergic neurons innervate many brain regions where they influence a wide variety of behaviours. However, the precise role of each cholinergic region on distinct types of behaviour is not well known. Furthermore, in recent years there has been evidence that many cholinergic neurons in the brain have a capacity for co-transmission. Yet the functional significance of secreting two classical neurotransmitters from the same neuron is still largely unidentified. In this thesis, we investigated how different cholinergic nuclei modulate behavioural functions. To …

Neural Substrates Of Reward, Error, And Effort Processing Underlying Adaptive Motor Behaviour, Dimitrios J. Palidis

Electronic Thesis and Dissertation Repository

Human motor control is highly adaptive to new tasks and changing environments. Motor adaptation relies on multiple dissociable processes that function to increase attainment of reward and to reduce sensory error and physical effort as costs. This thesis tests the hypothesis that fronto-striatal and dopaminergic neural systems contribute to specific aspects of motor adaptation that occur through reinforcement of rewarding actions.

Behavioral tasks were designed to isolate learning in response to feedback conveying information about reward, error, and physical effort. We also measured behavioral effects of savings and anterograde interference, by which memories from previous motor learning can facilitate or …

Dopamine-Dependent Task Performance Over The Menstrual Cycle, Alexandra A. De La Rua

Electronic Thesis and Dissertation Repository

Estradiol (E2) has been found to influence dopamine (DA) activity in the nonhuman animal brain. While there has been very little research performed looking at E2’s effects on DA-related cognitive function in humans, recent research found that women tested during high E2 phases of the menstrual cycle had significantly better performance on a DA-dependent spatial working memory task, than women tested during the lowest E2 phase. The current study utilized the natural hormone fluctuations that occur over the menstrual cycle to determine if E2 is associated with DA-dependent task performance. Using a repeated measures design, 47 women completed a battery …

Mechanisms Underlying Executive Function Deficits, Sagar Jayawantrao Desai

Electronic Thesis and Dissertation Repository

In our daily life, we come across situations where we meet unanticipated challenges, we must take certain decisions, pay attention, be flexible and inhibit impulsive actions to achieve goal directed behaviour. During these processes, we unknowingly use sets of interdependent cognitive processes collectively called ‘executive function’. Executive function is mainly regulated by the frontal lobe. Impaired executive function is associated with disorders such as schizophrenia, Alzheimer’s disease, autism and attention deficit hyperactivity disorder (ADHD).

In this thesis, we investigated neurotransmitters and interactions among them regulating executive function. Further, we investigated mechanisms underlying those interactions mediating executive function in rats using …

Prefrontal Cortex Dopamine Transmission Regulates Emotional Memory Processing And Morphine Reward Salience: Implications For Post-Traumatic Stress Disorder And Addiction Comorbidity, Jing Jing Li

Electronic Thesis and Dissertation Repository

Post-Traumatic Stress Disorder (PTSD) and addiction are strongly comorbid. However, the underlying neural mechanisms by which traumatic memory recall may increase addiction liability are poorly understood. The inability to suppress memory recall related to either stressful or rewarding, drug-related experiences may be an underlying neuropsychological feature capable of triggering both PTSD or addiction-related behaviours. Our previous research has shown that transmission through dopamine (DA) D₄ and D₁ receptor subtypes (D₄R, D₁R) within the prefrontal cortex (PFC) strongly modulates emotional memory acquisition and recall (Lauzon et al., 2009). Using olfactory fear conditioning and morphine conditioned …

Cannabinoid Cb1 Transmission In The Mesolimbic Reward Pathway, Tasha Ahmad

Electronic Thesis and Dissertation Repository

Cannabinoid CB1 receptor (CB1R) transmission within the mesocorticolimbic system plays an important role in forming associative memories, and processing both positive and negative experiences. Opiates generally produce potent rewarding effects and previous evidence suggests that CB1 transmission may modulate the neural reward circuitry involved in opiate reward processing. The ventral tegmental area (VTA), medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and Nucleus Accumbens (NA) are all implicated in opiate-reward processing, contain high levels of CB1 receptors, and are all modulated by dopamine (DA). Although, CB1 transmission within these areas has been heavily implicated in associative memory and learning, the potential …

Associations Between Hypothalamic-Pituitary-Adrenal Axis System Gene Variants And Cortisol Reactivity In Preschoolers: Main Effects And Gene-Environment Interactions, Haroon I. Sheikh

Electronic Thesis and Dissertation Repository

Exposure to stressful events during early development has consistently been shown to produce long lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis, which may increase vulnerability to mood and anxiety disorders. Recently reported genetic association studies indicate that these disorders may be influenced, in part, by gene-environment interactions (GxE) involving polymorphisms within the corticotrophin-releasing hormone and monoaminergic system genes. However, little is known about how genetic variants and life stress work to shape children’s neuroendocrine reactivity and emerging symptoms. Therefore, the aim of this thesis is to examine main effects of candidate genes and GxE on the neuroendocrine stress response and …

Cortical Cannabinoid Modulation Of Subcortical Dopamine Activity: Implications For Emotional Processing, Brittany Draycott

Electronic Thesis and Dissertation Repository

Humans receive countless sensory inputs from the outside world to which they assign a certain level of emotional significance. However, there are times when an individual may assign an abnormally high level of emotional salience to an otherwise non-significant event, resulting in an inappropriate allocation of attention as seen in the hallucinations and psychosis associated with schizophrenia. Several brain regions are involved in this emotional processing, including the medial prefrontal cortex (mPFC) and the ventral tegmental area (VTA). We have previously shown that activation of mPFC cannabinoid (CB1) receptors in rats causes a potentiated fear response to a normally non-salient …

Dopamine Modulation Of Emotional Learning In The Medial Prefrontal Cortex, Nicole M. Lauzon

Electronic Thesis and Dissertation Repository

Dopamine (DA) transmission plays a critical role in the processing of emotionally salient information and in associative learning and memory processes. Within the mammalian brain, neurons within the medial prefrontal cortex (mPFC) are involved critically in the encoding, expression, and extinction of emotionally salient learned information. Within the mPFC, DAergic transmission is involved importantly in controlling attention related and motivational processes, particularly within the context of emotionally salient sensory information. Considerable evidence suggests differential roles for DA D₁-like versus D₂-like receptors, including the D₄-receptor subtype, in the regulation of neuronal activity and emotional processing …

Circadian Rhythms In Reward And Underlying Neural Circuits, Ricardo M. Baltazar

Electronic Thesis and Dissertation Repository

Studies suggest that the circadian timing system exerts an important influence on responses to rewarding stimuli. Diurnal rhythms in the rewarding value of amphetamine and mating behavior were observed, but differed in the pattern of their timing. Daily fluctuations in reward were correlated with oscillations in mesolimbic dopaminergic activity in both the nucleus accumbens (NAc) and ventral tegmental area (VTA), with a peak in NAc coinciding with the peak of sex reward, while the peak in the VTA associated with the peak in amphetamine reward. Also, rhythmic expression of the marker of neural activation, cFos, was observed in NAc, medial …