The effects of dopamine D1 and D2 antagonists on conditioned place preference (CPP) and locomotor activity were assessed. A total of three experiments were conducted. In each experiment there were two conditioning days followed by a test day. The results indicate that DA D1 and D2 receptors have distictly different roles in the mediation of behavior.

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This investigation was an analysis of the effects of methylphenidate (MPH; trade name: Ritalin) on drug reward using the conditioned place preference (CPP) behavioral paradigm in a rodent model and underlying mechanisms of this effect. Animals were conditioned in adolescence from postnatal day (P)33-39) or P44-49 with saline, 1 or 5 mg/kg MPH. Rats administered 5 mg/kg but not 1 mg/kg MPH, resulted in a significant preference that was more robust in younger male adolescent rats. The 5 mg/kg dose of MPH also resulted in a significant decrease of the dopamine transporter in both the nucleus accumbens and striatum, revealing dopamine clearance is decreased by MPH in brain areas that mediate reward. Finally, MPH-induced CPP was blocked by the dopamine D1 but not D2 antagonist, demonstrating the importance of the D1 receptor in the rewarding effects of MPH. These results demonstrate that dopamine mediates the rewarding effects of MPH in adolescence.

Animal behaviours are demonstrably governed by sensory stimulation, previous experience and internal states like hunger. With increasing hunger, priorities shift towards foraging and feeding. During foraging, flies are known to employ efficient path integration strategies. However, general long-term activity patterns for both hungry and satiated flies in conditions of foraging remain to be better understood. Similarly, little is known about how permanent contact chemosensory stimulation affects locomotion. To address these questions, we have developed a novel, simplistic fly activity tracking setup— the Panopticon. Using a 3D-printed Petri dish inset, our assay allows recording of walking behaviour, of several flies in parallel, with all arena surfaces covered by a uniform substrate layer. We tested two constellations of providing food: (i) in single patches and (ii) omnipresent within the substrate layer. Fly tracking is done with FIJI, further assessment, analysis and presentation is done with a custom-built MATLAB analysis framework. We find that starvation history leads to a long-lasting reduction in locomotion, as well as a delayed place preference for food patches which seems to be not driven by immediate hunger motivation.

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Recent clinical and preclinical reports have identified traumatic brain injury (TBI) as an important risk factor affecting the development of substance use disorders (SUDs). Notably, these studies show that factors like age at the time of injury and TBI severity may increase the risk of substance abuse behavior post-TBI. Furthermore, radiological assessments in clinical TBI populations have observed neuropathology in select brain regions that form key neurocircuits that mediate drug reward and drug-seeking behavior. Therefore, the effects of TBI on the function of these brain structures may influence the risk of substance abuse behavior following brain injury. In order to test the effect of experimental TBI on substance abuse behavior, we utilized two premiere preclinical models: 1) the controlled cortical impact (CCI) model of experimental TBI and 2) a biased, three-phase, cocaine conditioned place preference (CPP) assay. Furthermore, we characterized the effect of experimental TBI on / Pathology

Pharmacological treatment of neuropathic pain is still insufficient. Methylphenidate, a psychostimulant that increases the dopamine and noradrenaline levels, is commonly used for treating ADHD. There have been reports of changes in patients pain thresholds by ADHD patients treated with methylphenidate. The aim of the study is to examine if methylphenidate can affect peripheral neuropathic pain. Neuropathic pain has been modelled on laboratory rats by chronic constriction of the ischiatic nerve. The effect of methylphenidate on the evoked pain component was evaluated on control animals and on animals with neuropathic pain using reflex (plantar test, vonFrey test) and operanting test (thermal place preference). The effect of methylphenidate on the spontaneous components of pain was evaluated using the methods of conditioned place preference. This study has proven that methylphenidate in an applicable dose of 1 mg/kg has an antialodynic effect but does not act antinociceptively. This study further confirms that methylphenidate in low doses does not act as attractant and has no effect on spontaneous pain. The last part of the study compares the different methods for pain measurement and comes to the conclusion that the plantar test is not an adequate method for evaluating the effect of analgesics...

The amphetamine derivative, 3,4-methylenedioxymethamphetamine (MDMA), is a popular drug often taken by young adults at dance clubs or rave parties. Laser light shows, fast-paced electronic music, and hot crowded dance floors are characteristic of these events, and Ecstasy users report that the acute effects of the drug are potentiated by these stimulatory conditions. However, it remains largely unknown how environmental stimuli impact the neurochemical and physiological effects of MDMA. The aim of the first study presented in this dissertation was to investigate how auditory stimuli (music, white noise, and no additional sound) influence MDMA conditioned place preference (CPP), self-administration, and nucleus accumbens (NAcc) dopamine (DA) and serotonin (5-HT) responses. Findings revealed a significant CPP for animals exposed to white noise during MDMA conditioning trials. After self-administration of MDMA (1.5 mg/kg), NAcc DA and 5-HT were highest in rats exposed to music during the test session. The second study aimed to investigate the effects of ambient temperature (23°or 32°C) on long-term MDMA self-administration and neurochemical responses. Results indicated no difference in self-administration or locomotor activity rates for the high versus room temperature groups across sessions. However, MDMA (3.0 mg/kg) administered in high ambient temperature resulted in significantly greater NAcc serotonin release compared to when taken at room temperature, but no differences in dopamine response was determined between the two conditions. Overall, these results indicate that auditory and thermal stimuli can effect MDMA-induced behavioral and neurochemical responses. The last aim tested a novel apparatus and method for use in animal models of drug reinforcement. By combining traditional CPP and self-administration procedures, this approach provided more informative data and circumvented some inherent drawbacks of each method alone. In addition to confirming the ability to produce drug conditioned place preferences after short- and long-term experiments, the long-term version of the procedure revealed a significant positive relationship between lever response rate and CPP magnitude. Therefore, this experimental design can be used to identify subgroups of rats that may vary in sensitivity to drug motivational effects. Further study of these populations may be useful in the development of behavioral and pharmacological therapies for drug addiction. / text

In the field of drug addiction, relapse back to drug seeking and taking is the major unmet clinical need. The rate of relapse back to drug-taking is ~70-80% within a year of drug abstinence. Gaining a better understanding of the prolonged neuronal changes that have taken place during drug addiction may lead to the design of better anti-relapse therapies. It is now widely believed that one component of drug addiction is by aberrant learning and memory processes. To study this, we investigated synaptic changes caused by the development of drug-seeking behaviour in C57BL/6J mice. Mice were treated either with non-contingent morphine or trained to exhibit drug-seeking behaviour following morphine-induced conditioned place preference (CPP) training, hippocampal slices were taken from these animals and synaptic changes examined at the CA3-CA1 synapse using electrophysiological methods. Mice that underwent morphine CPP were demonstrated to exhibit a significant preference for the morphine paired compartment before ex vivo electrophysiological analysis. Using field recordings, both non-contingent morphine and morphine CPP treatments resulted in a reduced ability to undergo stimulus-induced LTP compared to their respective controls. Whole cell patch clamp was then utilised to further investigate these effects. Non-contingent morphine treatment resulted in both pre- and post-synaptic changes with an increased AMPA:NMDA receptor ratio, concurrent increases in cell size, and reductions in the release probability of both glutamate and GABA. Morphine CPP treatment resulted in a more variable increase in AMPA:NMDA receptor ratio (presumably by the same mechanism but in a more specific group of neurones) and GABA release probability was also decreased. There were no detected increases in cell size however, or any detected changes in glutamate release probability. These findings therefore reveal a set of synaptic adaptations in the hippocampus unique to morphine-induced behavioural change, and may provide targets for future intervention in drug addiction.