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PSYC 2920 Lecture 4

PSYC 2920 Lecture 4. Tolerance, Withdrawal, Sensitization, and Conditioning of Drug Effects. Sensitization Sensitization or Reverse Tolerance An effect of a drug increases with repeated administrations

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PSYC 2920 Lecture 4

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  1. PSYC 2920Lecture 4

  2. Tolerance, Withdrawal, Sensitization, and Conditioning of Drug Effects • Sensitization • Sensitization or Reverse Tolerance • An effect of a drug increases with repeated administrations • An important component of drug-seeking behaviour according to the incentive-sensitization theory of addiction. • Sensitization and tolerance may both operate on different features of a drug at the same time! • Cross Sensitization • Mesolimbic dopamine system • Applies to certain aspects (e.g. locomotor output) of many drugs of abuse.

  3. Koob et al. Neuron, Vol. 21, 467–476, September, 1998

  4. Siegel Experiment Tolerance phase: Rats were given 30 daily injections of either heroin or placebo Group 1 – Heroin in Room A and placebo in Room B alternately Group 2 – Placebo in Room A and Heroin in Room B alternately Group 3 – Placebo in both room A and B alternately Testing Phase: All rats were given lethal dose of heroin (15 mg/Kg) ST rats were given Heroin in the same room they had received heroin previously DT rats were given Heroin in a different room from which they had received heroin Control rats were given Heroin in either room.

  5. Siegel Experiment • Results: • Control group - 96% died of overdose • no tolerance • ST group – 32% died of an overdose • tolerance • DT group – 64% died of overdose • partial tolerance – no conditioned tolerance

  6. Neurophysiology, Neurotransmitters, and the Nervous System • The Neuron • Resting Potential • Potential difference across the membrane • Voltmeter • measures differences in electrical potential • Ions • possess an electrical charge • Active transport mechanism/ion pump • Electrostatic charge • Ionophores/ion channels

  7. The Neuron

  8. Neurophysiology, Neurotransmitters, and the Nervous System • Resting Potential

  9. The Action Potential Process • Cells are at polarized resting state (-70 mV) • Excitatory & inhibitory inputs change the balance of ions inside the cell membrane • Excitatory = positive ions enter cell making it less negative • Inhibitory = make the cell more negative by keeping out + ions

  10. The Action Potential Process • Excitatory inputs lead to depolarization • When reaches -55 mV (threshold), action potential reached • During action potential, sodium ions (+) rush into cell and fully depolarize it • Domino effect as AP stimulates adjacent areas on axon (successive depolarization) • Cell membrane actively expels positive ions and becomes more negative than resting state during refractory period

  11. Neural Communication • Synapse • Junction between terminal of sending neuron and dendrite or cell body of receiving neuron • Tiny gap at this junction is called synaptic gap or cleft • Presynaptic = terminal button of sending neuron • Postsynaptic = dendrite of receiving neuron

  12. The Synapse

  13. Neurotransmitters • Chemical messengers that traverse synaptic gaps between neurons • When released by sending neuron, neurotransmitters travel across synapse and bind to receptor sites on receiving neuron, thereby influencing whether it will generate neural impulse • Reuptake: Neurotransmitters in synapse reabsorbed into sending neurons • Degradation: Neurotransmitters in synapse are destroyed by enzymes in the synapse

  14. Neural Communication

  15. The Synapse • Excitation • Excitory postsynaptic potential (EPSP) • Depolarization of the postsynaptic membrane • Inhibition • Inhibitory postsynaptic potential (IPSP) • Harder for the cell to produce action potentials • The summation of inhibitory and excitatory synaptic inputs determines if the cell will fire • Summation of Excitation and Inhibition • Spatial summation • 2 0r more neurons release transmitters onto the same target neuron • Temporal summation • Neuron produces several action potentials close in time

  16. Neurophysiology, Neurotransmitters, and the Nervous System The Synapse • A receptor gated ion channel in the closed configuration. • A transmitter molecule occupying the receptor site and the channel in the open configuration.

  17. Neurophysiology, Neurotransmitters, and the Nervous System • The Synapse • Summation of Excitation and Inhibition • Spatial summation • Two or more neurons release transmitters onto the same target neuron • Temporal summation • Neuron produces several action potentials close in time

  18. Neurophysiology, Neurotransmitters, and the Nervous System • The Synapse • Speed and Duration of the Effects of Neurotransmitters • Second Messengers • Chain of intracellular events that lead to short or long term changes in the cell

  19. Neurophysiology, Neurotransmitters, and the Nervous System • How Second Messengers Work

  20. Neurophysiology, Neurotransmitters, and the Nervous System • Relation between a signal cascade and the resulting effects on cell excitability.

  21. Neurophysiology, Neurotransmitters, and the Nervous System • The Synapse • Presynaptic Effects of Neurotransmitters • autoreceptors • Neuromodulators • Other Chemical Signaling Between Neurons • Depolarization-induced suppression of excitation • Depolarization-induced suppression of inhibition • Axo-axonal synapses

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