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The Journal of Neuroscience, March 24, 2004 24(12):3031 3039 3031 Cellular/Molecular Opioids Inhibit Lateral Amygdala Pyramidal Neurons by Enhancing a Dendritic Potassium Current E. S. Louise Faber1,2

E. MDA) that release inhibitory neurotransmitters (endogenously generated excitatory glutamatergic and Allergic synaptic currents), and have been implicated in the cognitive effects of substance abuse and alcohol withdrawal, schizophrenia, depression, post-traumatic stress disorder, attention deficit disorder, and cocaine- and amphetamine-induced loco motor sensitization. The effect of alcohol (A) and opioids (O) on lateral amygdala pyramidal neuron firing and transmitter release, the ability of these substances to alter activity-dependent plasticity in the lateral amygdala, and their impact on the learning and memory processes underlying drug and alcohol abuse and withdrawal, are reviewed. Findings of experiments and mechanistic studies are summarized, which identify the functional significance of the pyramidal neuron firing and transmitter release in regulating learning and memory processes involved in substance abuse and alcohol withdrawal. The potential mechanisms by which the two groups of agents modify the pyramidal neuron firing and transmitter release include GABAergic-GABAergic signaling, synaptic inhibition, TAMPA receptor mediated excitatory postsynaptic currents, calcium-dependent activation of intracellular signaling cascades, and calcium-independent intracellular signaling. Recent advances in understanding the physiological and behavioral effects of cocaine (COC) use, including studies suggesting that this compound may exert its behavioral effects via altering transmitter release in brain areas that have a direct impact on drug reward, and that these differences occur after chronic administration of cocaine but are abolished by the MDA antagonists, suggest that the findings presented here may have therapeutic implications. However, the use of opioids for the treatment of substance abuse is more controversial. Further research is required to determine the effects of opioids on brain cells in regions implicated in substance abuse as they may potentially have different mechanisms of action, possibly involving different classes of Allergic or glutamatergic receptors and differing responses to drug treatment. This work also will assist in identifying if certain classes of endogenous substances, such as drugs of abuse and alcohol, which are endogenously produced in different tissues and may exert effects in brain areas implicated in drug abuse or alcohol dependence also regulate transmitter release and the ability to inhibit pyramidal neurons using receptor subtypes. Introduction Substance abuse (DA), or the habitual use of substances other than alcohol for pleasure and social or work-related social benefits, is a major public health concern in many developed societies.[1] The term “substance abuse” (i.e.

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