Intermittent Cocaine Self‐Administration but not Passive Cocaine Infusions Reduces H‐Current in Putative Dopaminergic Neurons of the Ventral Tegmental Area

Abstract

Intermittent Access (IntA) cocaine self‐administration is a protocol suggested to better simulate human drug use patterns due to its temporal dynamics of drug administration. IntA is also known to produce incentive salience and psychomotor sensitization. Dopaminergic (DA) neurons display a prominent mixed cation current conductance known as the hyperpolarization‐activated cyclic nucleotide current, or Ih, which contributes to neural processes such as resting membrane potential, firing frequency modulation, and synaptic integration. Previous results from our laboratory demonstrated that Ih amplitude is reduced significantly after cocaine sensitization. This Ih reduction resulted in an increased temporal summation, mean depolarization, and excitatory postsynaptic potential (EPSP) amplitude, all factors related to an enhanced excitability state. Since the cocaine sensitization model involves noncontingent drug injections administered by the experimenter, it is crucial to determine if electrophysiological changes in ventral tegmental area (VTA) DA cells are present when drugs are self‐administered (contingent). In the present study, we explored if DA neurons present an alteration in Ih after exposure to IntA. We hypothesize that VTA DA cells’ Ih modulation is dependent on the associative learning processes acquired during operant conditioning. Using the whole‐cell patch‐clamp technique in brain slices, we investigated the effects of cocaine IntA, and passive cocaine infusions (yoked controls) on Ihamplitude and rebound excitability. Our results demonstrate that an IntA protocol, but not passive cocaine infusions, produces a significant Ih amplitude reduction (P<0.05). No differences in rebound action potentials (APs) were observed. A depolarizing current protocol showed a significant increase in the number of APs (P<0.05). These results suggest that Ih modulation and intrinsic activity regulation are dependent on associative learning to drug cues.