BIOL 2P94 Lecture Notes - Lecture 7: Limbic System, Cyclic Adenosine Monophosphate, Transporter Reversal

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Outline of Lecture 73 (03-31 B; Molliver)
You might want to review Lectures 22 (Monoamines II) and 51 (Basal Ganglia).
Effects of stimulant drugs is the focus of this lecture
- Dopamine neurons are found in ventral tegmentum (midbrain)
- Basic structure of a basal ganglia loop is the same for neocortex and limbic system
- Neocortex dorsal striatum (caudate) globus pallidus VA thalamus
- Hippocampus ventral striatum (nucleus accumbens) ventral pallidum (substantia
innominata) MD thalamus anterior cingulate/orbitofrontal cortex
- The basal ganglia provides the connection between limbic system and dopamine neurons
- Recall from basal ganglia lecture that DA neurons from ventral tegementum area project to
striatum and substantia nigra; therefore DA neurons can affect the limbic system through
its basal ganglia loop
- DA neurons exert their effects by modulating postsynaptic response to Glu (D1 facilitates, D2
- Serotonin neurons are found in the raphe nuclei (midbrain) and project to forebrain via the
medial forebrain bundle
III. Molecular mechanism of stimulant action
- Serotonin or DA release via stimulant drugs is nonphysiologic
- For example, amphetamines (1) reverse the plasma membrane transporter and (2) inhibit the
vesicular transporter (causes high nxt conc. in cytoplasm, driving plasma membrane
transporter reversal)
- Cocaine blocks reuptake and causes nxt accumulation in the synapse
- High levels of amphetamine causes loss of 5-HT axons/neurons
- Addiction may be mediated by LTP
- In this case, the LTP is manifested as increased AMPA response to Glu
- DARPP-32 is a transcription factor regulated by cAMP that may be involved in this
Summary of major ideas
- Understand how dopamine affects the limbic system through the basal ganglia
- Know the locations of DA and 5-HT neurons
- Know how stimulants cause DA or 5-HT release through an unusual nonphysiologic process
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