Acute Cocaine Exposure elicits rises in calcium in Arousal Related Laterodorsal Tegmental Neurons

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Cocaine has strong reinforcing properties, which underlie its high addiction potential. Reinforcement of use of addictive drugs is associated with rises in dopamine (DA) in mesoaccumbal circuitry. Excitatory afferent input to mesoaccumbal circuitry sources from the laterodorsal tegmental nucleus (LDT). Chronic, systemic cocaine exposure has been shown to have cellular effects on LDT cells, but acute actions of local application have never been demonstrated. Using calcium imaging, we show that acute application of cocaine to mouse brain slices induces calcium spiking in cells of the LDT. Spiking was attenuated by tetrodotoxin (TTX) and low calcium solutions, and abolished by prior exhaustion of intracellular calcium stores. Further, DA receptor antagonists reduced these transients, whereas DA induced rises with similar spiking kinetics. Amphetamine, which also results in elevated levels of synaptic DA, but via a different pharmacological action than cocaine, induced calcium spiking with similar profiles. Although large differences in spiking were not noted in an animal model associated with a heightened proclivity of acquiring addiction-related behavior, the prenatal nicotine exposed mouse (PNE), subtle differences in cocaine's effect on calcium spiking were noted, indicative of a reduction in action of cocaine in the LDT associated with exposure to nicotine during gestation. When taken together, our data indicate that acute actions of cocaine do include effects on LDT cells. Considering the role of intracellular calcium in cellular excitability, and of the LDT in addiction circuitry, our data suggest that cocaine effects in this nucleus may contribute to the high addiction potential of this drug.
Original languageEnglish
Article numbere00282
JournalPharmacology Research and Perspectives
Issue number1
Number of pages23
Publication statusPublished - 2017

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