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Intermittent Cocaine Self‐Administration Infusions Increases Subthreshold Activity in Putative Dopaminergic Neurons of The Ventral Tegmental Area
Author(s) -
Calo Cristhian G.,
Velez Omaris,
Bosque Karl,
Consuegra Daisy,
Vazquez Rafael,
JimenezRivera Carlos A.
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r6213
Subject(s) - ventral tegmental area , neuroscience , excitatory postsynaptic potential , chemistry , hyperpolarization (physics) , dopamine , membrane potential , dopaminergic , neurochemical , electrophysiology , nucleus accumbens , sensitization , psychology , inhibitory postsynaptic potential , nuclear magnetic resonance spectroscopy , organic chemistry
Intermittent Access (IntA) cocaine self‐administration is a protocol suggested to better simulate human addictive behavior due to the intermittent pattern of drug administration. IntA is also known to produce incentive salience and psychomotor sensitization. It is documented that IntA produces a neurochemical sensitization of the mesolimbic dopamine (DA) system by increasing both release and uptake of DA. The ventral tegmental area (VTA) DA neurons display a prominent mixed cation current conductance known as the hyperpolarization‐activated cyclic nucleotide current, or I h . Neural processes such as resting membrane potential, firing frequency modulation, and synaptic integration are influenced by the I h . Previous results from our laboratory demonstrated that I h amplitude and membrane capacitance of putative VTA DA neurons are significantly reduced after cocaine sensitization. This I h and capacitance reduction resulted in an increased temporal summation, mean depolarization and excitatory postsynaptic potential (EPSP) amplitude, all related to an enhanced neuronal excitability state. It is not known how IntA alters the intrinsic properties of VTA DA cells. Since the cocaine sensitization model involves experimenter administered drug injections (non‐contingent) it is important to determine if electrophysiological changes in VTA DA cells are present when drugs are self‐administered (contingent). In the present study we explored if synaptic integration, membrane capacitance and cell activity alterations are present after exposure to cocaine IntA. Our hypothesis is that IntA enhances synaptic integration and neuronal excitability of VTA DA cells. Whole‐cell patch‐clamp technique in rat brain slices was used to inject a 33‐Hz train of 5 αEPSCs (α = 5 ms; Imax = 50) into the soma of putative VTA DA neurons when clamped at ‐70 mV and analyze the effects of cocaine IntA, and passive cocaine infusions (yoked controls) on synaptic integration. Increasing depolarizing current injections were used to evaluate how neurons respond to a depolarizing stimulus. Our results demonstrate that an IntA protocol, but not passive cocaine infusions, produces a significant increase in the number of APs (P<0.05). Temporal summation was increased at depolarized potentials in the IntA group and Yoked controls (P<0.0001). These results suggests that neuronal activity regulation is dependent on associative learning to drug cues. The findings also suggest that enhanced synaptic integration could possibly be a cocaine‐induced pharmacological effect.