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The Opponent Consequences of Intermittent and Continuous View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Texas A&M University THE OPPONENT CONSEQUENCES OF INTERMITTENT AND CONTINUOUS STIMULATION WITHIN THE RAT SPINAL CORD A Thesis by DENISE ALEJANDRA PUGA Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE August 2007 Major Subject: Psychology THE OPPONENT CONSEQUENCES OF INTERMITTENT AND CONTINUOUS STIMULATION WITHIN THE RAT SPINAL CORD A Thesis by DENISE ALEJANDRA PUGA Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Approved by: Chair of Committee, James Grau Committee Members, Mary Meagher Rajesh Miranda Head of Department, Les Morey August 2007 Major Subject: Psychology iii ABSTRACT The Opponent Consequences of Intermittent and Continuous Stimulation within the Rat Spinal Cord. (August 2007) Denise Alejandra Puga, B.A., New Mexico State University Chair of Advisory Committee: Dr. James W. Grau A substantial body of work exists to suggest that brain and spinal mechanisms react differently to nociceptive information. The current experiments were design to identify parallels and differences in the way the spinal cord processes nociceptive information, as compared to intact animals. In addition, pharmacological manipulations were employed to identify the opioid receptors activated by continuous shock, and to decipher at what synaptic level (e.g. pre or post synaptically) intermittent shock affects the release of endogenous opioids. A common dependent variable was used in all experiments to assess changes in nociceptive reactivity, the tail-flick test. The results revealed that intermittent and continuous stimulation have an opponent relationship on nociceptive processing in the isolated spinal cord. Continuous stimulation (3, 25-s continuous 1.5 mA tail-shocks) induced an antinociceptive response that was attenuated by prior exposure to brief (80 ms) intermittent shock (Experiment 1). When intermittent shock was given after continuous shock, intermittent shock failed to attenuate continuous shock-induced antinociception (Experiment 2). The impact of intermittent shock on continuous-shock induced antinociception decayed after 24 hours (Experiment 3). Intermittent and continuous shock enhanced the antinociceptive iv consequences of a moderate dose of systemic morphine (5 mg/kg) (Experiment 4). Continuous shock-induced antinociception was attenuated by equal molar concentrations of CTOP (µ opioid antagonist) and Nor-BNI (κ opioid antagonist), but not naltrindole (δ opioid antagonist) (Experiment 5). Intermittent shock failed to attenuate the antinociception induced by DAMGO (µ opioid agonist) or Dynorphin A (κ opioid agonist). v DEDICATION I would like to dedicate this thesis, first and foremost, to my parents, Mr. and Mrs. Roberto and Alba Puga, for their infinite supply of love and guidance. I would also like to dedicate this thesis to my sisters, Christina and Pamela Puga, for allowing me the privilege and honor of being their “big sister”; and to my best friend, Eunice Saldaña, who has always been an outstanding accomplice and confidant. vi ACKNOWLEDGEMENTS I would like to thank Dr. James W. Grau for his support, guidance, and mentorship. Without his vision and empirical knowledge, this project would not have been possible. I would also like to thanks Drs. Mary W. Meagher and Rajesh Miranda for serving as committee members. Finally, I would like to thank Dr. Michelle A. Hook, Dr. Kyle M. Baumbauer, Dr. Stephanie N. Washburn, Russell Huie, and Kevin Hoy for providing an unbelievable working environment, where science is a joy to discover. vii TABLE OF CONTENTS Page ABSTRACT......................................................................................................... iii DEDICATION ..................................................................................................... v ACKNOWLEDGEMENTS.................................................................................. vi TABLE OF CONTENTS...................................................................................... vii LIST OF FIGURES.............................................................................................. ix INTRODUCTION................................................................................................ 1 GENERAL METHOD.......................................................................................... 5 Subjects ................................................................................................... 5 Surgery ................................................................................................... 5 Apparatus ................................................................................................ 6 Statistics .................................................................................................. 7 EXPERIMENT 1.................................................................................................. 8 Procedure .............................................................................................. 8 Results .................................................................................................. 9 Discussion ............................................................................................. 10 EXPERIMENT 2.................................................................................................. 11 Procedure .............................................................................................. 11 Results .................................................................................................. 1 1 Discussion ............................................................................................. 11 EXPERIMENT 3.................................................................................................. 13 Procedure .............................................................................................. 13 Results .................................................................................................. 1 3 Discussion ............................................................................................. 15 EXPERIMENT 4.................................................................................................. 16 Procedure .............................................................................................. 16 viii Page Results .................................................................................................. 1 6 Discussion ............................................................................................. 19 EXPERIMENT 5.................................................................................................. 20 Procedure .............................................................................................. 20 Results .................................................................................................. 2 0 Discussion ............................................................................................. 22 EXPERIMENT 6.................................................................................................. 24 Procedure .............................................................................................. 24 Results .................................................................................................. 2 4 Discussion ............................................................................................. 26 CONCLUSIONS .................................................................................................. 27 Clinical Implications .............................................................................. 3 0 REFERENCES..................................................................................................... 33 VITA.................................................................................................................... 38 ix LIST OF FIGURES FIGURE Page 1 Tail-flick latencies significantly increased from baseline after 3, 25-s continuous tailshocks .............................................. 9 2 Intermittent shock failed to attenuate increases in test tail-flick latencies when intermittent shock was given after continuous shock .................................................................... 12 3 Exposure to six minutes of intermittent shock, or an equivalent period of restraint, did not induce an increase in tail-flick latencies...................................................................................... 14 4 Morphine (5mg/kg) and saline unshocked rats did not show an increase in tail-flick latencies .......................................... 17 5 Mean tail-flick latencies for all groups ..................................................... 18 6 Saline rats exposed to 3, 25-s continuous tailshocks showed an increase in tail-flick latencies................................................... 21 7 Intermittent shock did not produce an increase in tail-flick latencies...................................................................................... 25 1 INTRODUCTION Exposure to aversive stimuli, such as electrical shock, induces an antinociceptive response in intact rats. This finding suggests that pain is not an inevitable consequence of noxious stimulation; instead, nociceptive information is filtered by mechanisms in the central nervous
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