The Role of Dopamine and Glutamate in Associative Learning by the Pigeon (Columba livia)

7 Chapter I A general introduction 13 Learning and memory 14 Classical conditioning 15 The context as a CS 16 Drug action as a US 16 Discrimination learning 17 Dopamine in learning 18 The Wickens' learning model 20 The hypothesis 22 Chapter II The glutamatergic and dopaminergic systems. The glutamatergic system Glutamate based transmission 25 Glutamate synthesis 26 Glutamate receptors 26 Glutamate pathways 29 LTP and glutamate NMDA receptors 33 Pharmacology of NMDA receptors 34 The dopaminergic system Dopaminergic based transmission 36 Dopamine receptors 38 Dopamine in the CNS 41 Pharmacology of the dopaminergic system 43 Apomorphine 44 Dopamine in the spinal cord of pigeon 46 Experiment 1 49 Methods 49 Results 50 TH-immunoreactive cells 52 DA-immunoreactive cells 52 DARPP-32-immunoreactive cells 54 Discussion 55 Pre-synaptic membrane 55 Post-synaptic membrane 58 Dopaminergic functionality in the pigeon' spinal cord 59 Chapter III Conditioning induced by apomorphine Introduction 61 Apomorphine induces stereotyped activity 62 Apomorphine induces behavioural sensitisation 64 The mechanism of apomorphine-induced pecking sensitisation 65 The apomorphine-context conditioning experimental situation 67 Standard curves of apomorphine-induced sensitisation and saline control 69 Learning leads to memory 72 Long-term retention of the apomorphine-context association Experiment 2 73 Method 73 Results 74 Conclusion 76 Chapter IV Dopamine receptor changes consequent upon sensitisation to apomorphine Introduction 79 Biochemical modification of the dopamine receptors Experiment 3 80 The radioligand binding assay technique 82 Equations and parameters of the binding assay technique 82 Tissue preparation 85 Method 85 Results and discussion 87 Local administration of apomorphine into the pigeon's brain Experiment 4 90 Method 90 Cannuli 91 Procedure 91 Histology 93 Results and discussion 93 General discussion 95 Chapter V A novel drug-free associative learning An association between coloured grit and food. Introduction 99 Simultaneous discrimination of a visual stimulus Experiment 5 101 Method 101 The cage 101 Procedure 102 Analysis 104 Results First phase 105 Second phase 107 Discussion First phase 111 Second phase 112 Chapter VI Role of dopamine and glutamate during the grit-food association. Introduction 117 Effects of haloperidol on the coloured grit discrimination 119 Experiment 6 119 Method 119 Results Saline control group 120 Haloperidol groups 122 Discussion 123 Effects of SCH-23390 on the coloured grit discrimination Experiment 7 126 Method 126 Results 128 Effects of MK-801 on the coloured grit discrimination Experiment 8 132 Method 132 Results 132 General discussion 135 Chapter VII Role of dopamine and glutamate in apomorphine-induced learning Introduction 139 The effects of haloperidol 141 Effect of haloperidol on forage pecking Experiment 9 142 Method 142 Results and conclusions 142 Effect of haloperidol on apomorphine-context association Experiment 10 143 Method 144 Results and conclusions 144 The effects of SCH-23390 146 Determination of the effective SCH-23390 dose Experiment 11 147 Method 147 Results and conclusions 148 Effects of SCH-23390 on forage pecking Experiment 12 151 Method 151 Results and conclusions 151 Effects of SCH-23390 on the apomorphine-context association Experiment 13 153 Method 153 Results and conclusions 154 The effects of the MK-801 156 Determination of the MK-801 dose Experiment 14 157 Method 157 Results and conclusions 157 Effects of MK-801 on forage pecking Experiment 15 158 Method 158 Results and conclusions 159 Effects of MK-801 on the apomorphine-context association Experiment 16 159 Method 160 Results and conclusions 161 Effects of MK-801 on the expression of the apomorphine-context association Experiment 17 164 Method 164 Results and conclusions 164 Chapter VIII General discussion General discussion 167 Unspecific drug effects 169 Hyper-sensitisation of apomorphine-induced pecking 171 Dopamine and learning 173 Glutamate and learning 176 Interaction dopamine-glutamate 178 Apomorphine-context paradigm and the Wickens' learning model 180 Apomorphine vs. simultaneous discrimination paradigm 182