Abstract
There is general agreement that dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens and prefrontal cortex play a key role in drug reinforcement. The activity of these neurons is strongly modulated by the inhibitory and excitatory input they receive. Activation of μ-opioid receptors, located on GABAergic neurons in the VTA, causes hyperpolarization of these GABAergic neurons, thereby causing a disinhibition of VTA dopaminergic neurons. This effect of μ-opioid receptors upon GABA neurotransmission is a likely mechanism for μ-opioid receptor modulation of drug reinforcement. We studied μ-opioid receptor signaling in relation to cocaine reinforcement in wild-type and μ-opioid receptor knockout mice using a cocaine self-administration paradigm and in vitro electrophysiology. Cocaine self-administration was reduced in μ-opioid receptor knockout mice, suggesting a critical role of μ-opioid receptors in cocaine reinforcement. The frequency of spontaneous inhibitory post-synaptic currents onto dopaminergic neurons in the ventral tegmental area was increased in μ-opioid receptor knockout mice compared with wild-type controls, while the frequency of spontaneous excitatory post-synaptic currents was unaltered. The reduced cocaine self-administration and increased GABAergic input to VTA dopaminergic neurons in μ-opioid receptor knockout mice supports the notion that suppression of GABAergic input onto dopaminergic neurons in the VTA contributes to μ-opioid receptor modulation of cocaine reinforcement.
Original language | English |
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Pages (from-to) | 359-367 |
Number of pages | 9 |
Journal | Neuroscience |
Volume | 130 |
Issue number | 2 |
DOIs | |
Publication status | Published - 31 Jan 2005 |
Keywords
- addiction
- cocaine
- dopamine
- GABA
- opioids
- ventral tegmental area