<p>Drug addiction and behavioural sensitization are associated with reorganization of mesolimbocortical circuitry, which we have attempted to model with glutamatergic-based long-term potentiation (LTP) in the medial prefrontal cortex (mPFC). The objective of the experiments was to examine the effects of dopamine-1 (01) and dopamine-2 (02) receptor family specific agonists and antagonists on LTP in the mPFC in the chronic in vivo preparation using fullyawake, freely-moving rats. Male Long-Evans rats were surgically implanted with stimulating electrodes into the corpus callosum and recording electrodes into the mPFC. Subjects were systemically administered a drug together with high frequency stimulation for the induction of LTP. The rats treated with the 0 1 receptor agonist A68930 (OAmg/kg/ml) showed LTP levels equal to those in the saline LTP group. The 0 1 receptor antagonist SKF83566 (0 . 15m~,/kg/ml) blocked the expression of LTP, and instead induced significant long-term depression. The 02 receptor antagonist sulpiride (3, 6, and 12mg/kg/ml) significantly decreased LTP, compared to the control group, in a dose-dependent fashion. The O2 receptor agonist quinpirole (0.125, 0.25, and 0.5mg/kg/ml) significantly increased LTP, compared to the control group, in a dose-dependent fashion. The O2 receptor agonist also induced behavioural sensitization, the intensity and frequency of which was positively correlated with the LTP effect. This is the first iii work to show that glutamatergic-based LTP in the mPFC is positively modulated by 02 receptors in the chronic in vivo preparation, and behavioural sensitization is, in turn, modulated by LTP induction. As O2 receptor-rich neurons are located largely in mesencephalic nuclei that, in turn, project to the mPFC, the 02 effects may be indirect. This plasticity modulation needs to be more deeply explored to determine its relationship to disorders, such as psychostimulant addiction and schizophrenia that are known to be due to dysregulated dopamime and glutamate function in the mesencephalon and mPFC.</p> / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/13672 |
| Date | January 2007 |
| Creators | Coppa-Hopman, Romina D. |
| Contributors | Racine, Ronald J., Psychology |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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