Self-Administration of Ethanol, Cocaine, or Nicotine Does Not Decrease the Soma Size of Ventral Tegmental Area Dopamine Neurons

Abstract

Our previous observations show that chronic opiate administration, including self-administration, decrease the soma size of dopamine (DA) neurons in the ventral tegmental area (VTA) of rodents and humans, a morphological change correlated with increased firing rate and reward tolerance. Given that a general hallmark of drugs of abuse is to increase activity of the mesolimbic DA circuit, we sought to determine whether additional drug classes produced a similar morphological change. Sections containing VTA were obtained from rats that self-administered cocaine or ethanol and from mice that consumed nicotine. In contrast to opiates, we found no change in VTA DA soma size induced by any of these other drugs. These data suggest that VTA morphological changes are induced in a drug-specific manner and reinforce recent findings that some changes in mesolimbic signaling and neuroplasticity are drug-class dependent.

Determination of circuit-specific morphological adaptations in ventral tegmental area dopamine neurons by chronic morphine

“…2a and b). Prior experiments that implanted subcutaneous morphine pellets for chronic morphine exposure exclusively used male rodents [32, 33, 41]. Therefore, we tested the drug administration paradigm in both sexes, and found no significant difference in free morphine (nM/g mouse) in isolated blood serum (Fig.…”

“…For soma size studies, VTA confocal z-stack images were taken using Olympus Fluoview FV1000 (version 4.2) and digital color camera (Olympus DP72) using a 60x PlanApoN (NA 1.42) oil objective and scan speed of 8.0 μs/pixel, Kalman average 4, step size 0.42 μm (Michigan State University Center for Advanced Microscopy). Following confocal imaging, neurons expressing either eYFP or mCherry (fluorescent protein, FP) were reconstructed in three dimensions and the surface area was measured using image analysis software (Volocity 3D Image Analysis Software, RRID:SCR_002668) as described previously [32, 33, 41]. We observed robust co-localization of TH protein (IHC) and viral-mediated fluorescent labeling with very few TH-negative, FP-positive neurons in the posterior lateral regions of the VTA (paranigral, PN and lateral portion of the PN) consistent with previous studies [44].…”

“…For example, following chronic morphine administration VTA DA neurons exhibit increased spontaneous and burst firing rates [23, 33] and a unique morphological adaptation, specifically an ~ 20–25% reduction in soma size [9, 33, 41, 43]. Given that this reduction can be blocked with opiate antagonists such as naltrexone [43] and that it does not occur following chronic administration of other commonly abused drugs such as cocaine, ethanol, or nicotine [32] suggests that this structural plasticity may be dependent on opioid signaling. Decreased VTA DA soma size has also been observed in post-mortem samples from heroin addicts, demonstrating translational relevance [33].…”

Comparison of chronic physical and emotional social defeat stress effects on mesocorticolimbic circuit activation and voluntary consumption of morphine

“…Physical and emotional CSDS was performed as described above. Mice underwent intracardial perfusion with 4% paraformaldehyde one-hour following SI testing on D1, and brains were post-fixed for 24 hr, cryoprotected in 30% sucrose and stored at 4 °C, per standard procedures 15 , 46 , 47 . Brains were sectioned (coronal, 35 µm), and selected brain regions were identified according to Paxinos G 48 .…”

Nicotine self‐administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats

“…However, little is known about the morphological and structural changes induced in the VTA after nicotine self-administration. While one study has shown that nicotine self-administration has no effect on the size of DA soma in VTA (Mazei-Robison et al, 2014), that study did not examine GABAergic input processes.…”