The tail of the ventral tegmental area in behavioral processes and in the effect of psychostimulants and drugs of abuse

2018 ◽  
Vol 84 ◽  
pp. 30-38 ◽  
Author(s):  
Marc Fakhoury
Keyword(s):  
Ventral Tegmental Area ◽  
Drugs Of Abuse ◽  
Ventral Tegmental

Restricted feeding with scheduled sucrose access results in an upregulation of the rat dopamine transporter

2003 ◽  
Vol 284 (5) ◽  
pp. R1260-R1268 ◽  
Author(s):  
Nicholas T. Bello ◽  
Kristi L. Sweigart ◽  
Joan M. Lakoski ◽  
Ralph Norgren ◽  
Andras Hajnal
Keyword(s):  
Ventral Tegmental Area ◽  
Drugs Of Abuse ◽  
Sucrose Solution ◽  
Male Rats ◽  
Mrna Levels ◽  
Restricted Feeding ◽  
Cellular Mechanisms ◽  
Dopamine System ◽  
Ventral Tegmental ◽  
Protein Density

Recent studies suggest that the mesoaccumbens dopamine system undergoes neurochemical alterations as a result of restricted feeding conditions with access to sugars. This effect appears to be similar to the neuroadaptation resulting from drugs of abuse and may underlay some pathological feeding behaviors. To further investigate the cellular mechanisms of these alterations, the present study used quantitative autoradiography and in situ hybridization to assess dopamine membrane transporter (DAT) protein density and mRNA expression in restricted-fed and free-fed adult male rats. The restricted feeding regimen consisted of daily limited access to either a normally preferred sucrose solution (0.3 M) or a less preferred chow in a scheduled (i.e., contingent) fashion for 7 days. Restricted-fed rats with the contingent sucrose access lost less body weight, ate more total food, and drank more fluid than free-fed, contingent food, or noncontingent controls. In addition, these animals had selectively higher DAT binding in the nucleus accumbens and ventral tegmental area. This increase in protein binding also was accompanied by an increase in DAT mRNA levels in the ventral tegmental area. In contrast to the restricted-fed groups, no differential effect in DAT regulation was observed across free-fed groups. The observed alteration in behavior and DAT regulation suggest that neuroadaptation in the mesoaccumbens dopamine system develops in response to repeated feeding on palatable foods under dietary constraints. This supports the notion that similar cellular changes may be involved in restrictive eating disorders and bingeing.

A-type K+ Current of Dopamine and GABA Neurons in the Ventral Tegmental Area

2006 ◽  
Vol 96 (2) ◽  
pp. 544-554 ◽  
Author(s):  
Susumu Koyama ◽  
Sarah B. Appel
Keyword(s):  
Ventral Tegmental Area ◽  
Current Density ◽  
Drugs Of Abuse ◽  
Physiological Role ◽  
Firing Frequency ◽  
Membrane Hyperpolarization ◽  
Gaba Neurons ◽  
Type K ◽  
Voltage Dependent ◽  
Ventral Tegmental

A-type K+ current ( IA) is a rapidly inactivating voltage-dependent potassium current which can regulate the frequency of action potential (AP) generation. Increased firing frequency of ventral tegmental area (VTA) neurons is associated with the reinforcing effects of some drugs of abuse like nicotine and ethanol. In the present study, we classified dopamine (DA) and GABA VTA neurons, and investigated IA properties and the physiological role of IA in these neurons using conventional whole cell current- and voltage-clamp recording. DA VTA neurons had a mean firing frequency of 3.5 Hz with a long AP duration. GABA VTA neurons had a mean firing frequency of 16.7 Hz with a short AP duration. For IA properties, the voltage-dependence of steady-state IA activation and inactivation was similar in DA and GABA VTA neurons. IA inactivation was significantly faster and became faster at positive voltages in GABA neurons than DA neurons. Recovery from inactivation was significantly faster in DA neurons than GABA neurons. IA current density at full recovery was significantly larger in DA neurons than GABA neurons. In DA and GABA VTA neurons, latency to the first AP after the recovery from membrane hyperpolarization (repolarization latency) was measured. Longer repolarization latency was accompanied by larger IA current density in DA VTA neurons, compared with GABA VTA neurons. We suggest that IA contributes more to the regulation of AP generation in DA VTA neurons than in GABA VTA neurons.

scholarly journals Opioid Facilitation of Rewarding Electrical Brain Stimulation Is Suppressed in Rats with Neuropathic Pain

2011 ◽  
Vol 114 (3) ◽  
pp. 624-632 ◽  
Author(s):  
Eric E. Ewan ◽  
Thomas J. Martin
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Electrical Stimulation ◽  
Ventral Tegmental Area ◽  
Drugs Of Abuse ◽  
Spinal Nerve ◽  
Abuse Liability ◽  
Prescription Opioid ◽  
Ventral Tegmental ◽  
Stimulation Of

Introduction Opioids are powerful analgesics, but are also common drugs of abuse. Few studies have examined how neuropathic pain alters the pharmacology of opioids in modulating limbic pathways that underlie abuse liability. Methods Rats with or without spinal nerve ligation (SNL) were implanted with electrodes into the left ventral tegmental area and trained to lever press for electrical stimulation. The effects of morphine, heroin, and cocaine on facilitating electrical stimulation of the ventral tegmental area and mechanical allodynia were assessed in SNL and control subjects. Results Responding for electrical stimulation of the ventral tegmental area was similar in control and SNL rats. The frequency at which rats emitted 50% of maximal responding was 98.2 ± 5.1 (mean ± SEM) and 93.7 ± 2.8 Hz in control and SNL rats, respectively. Morphine reduced the frequency at which rats emitted 50% of maximal responding in control (maximal shift of 14.8 ± 3.1 Hz), but not SNL (2.3 ± 2.2 Hz) rats. Heroin was less potent in SNL rats, whereas cocaine produced similar shifts in control (42.3 ± 2.0 Hz) and SNL (37.5 ± 4.2 Hz) rats. Conclusions Nerve injury suppressed potentiation of electrical stimulation of the ventral tegmental area by opioids, suggesting that the positive reinforcing effects are diminished by chronic pain. Given concerns regarding prescription opioid abuse, developing strategies that assess both analgesia and abuse liability within the context of chronic pain may aid in determining which opioids are most suitable for treating chronic pain when abuse is a concern.

scholarly journals Ethanol Effects on Dopaminergic Ventral Tegmental Area Neurons During Block of Ih: Involvement of Barium-Sensitive Potassium Currents

2008 ◽  
Vol 100 (3) ◽  
pp. 1202-1210 ◽  
Author(s):  
John McDaid ◽  
Maureen A. McElvain ◽  
Mark S. Brodie
Keyword(s):  
Potassium Channels ◽  
Firing Rate ◽  
Ventral Tegmental Area ◽  
Drugs Of Abuse ◽  
Potassium Conductance ◽  
Firing Frequency ◽  
Cationic Current ◽  
Ventral Tegmental ◽  
Ethanol Ethanol ◽  
Rats And Mice

The dopaminergic neurons of the ventral tegmental area (DA VTA neurons) are important for the rewarding and reinforcing properties of drugs of abuse, including ethanol. Ethanol increases the firing frequency of DA VTA neurons from rats and mice. Because of a recent report on block of ethanol excitation in mouse DA VTA neurons with ZD7288, a selective blocker of the hyperpolarization-activated cationic current Ih, we examined the effect of ZD7288 on ethanol excitation in DA VTA neurons from C57Bl/6J and DBA/2J mice and Fisher 344 rats. Ethanol (80 mM) caused only increases in firing rate in mouse DA VTA neurons in the absence of ZD7288, but in the presence of ZD7288 (30 μM), ethanol produced a more transient excitation followed by a decrease of firing. This same biphasic phenomenon was observed in DA VTA neurons from rats in the presence of ZD7288 only at very high ethanol concentrations (160–240 mM) but not at lower pharmacologically relevant concentrations. The longer latency ethanol-induced inhibition was not observed in DA VTA neurons from mice or rats in the presence of barium (100 μM), which blocks G protein–linked potassium channels (GIRKs) and other inwardly rectifying potassium channels. Ethanol may have a direct effect to increase an inhibitory potassium conductance, but this effect of ethanol can only decrease the firing rate if Ih is blocked.

Characterization of M-Current in Ventral Tegmental Area Dopamine Neurons

2006 ◽  
Vol 96 (2) ◽  
pp. 535-543 ◽  
Author(s):  
Susumu Koyama ◽  
Sarah B. Appel
Keyword(s):  
Action Potential ◽  
Ventral Tegmental Area ◽  
Neuronal Excitability ◽  
Drugs Of Abuse ◽  
Dopamine Neurons ◽  
M Current ◽  
Potential Shape ◽  
Voltage Dependent ◽  
Dependent Inhibition ◽  
Ventral Tegmental

M-current ( IM) is a voltage-gated potassium current (KCNQ type) that affects neuronal excitability and is modulated by some drugs of abuse. Ventral tegmental area (VTA) dopamine (DA) neurons are important for the reinforcing effects of drugs of abuse. Therefore we studied IM in acutely dissociated rat DA VTA neurons with nystatin-perforated patch recording. The standard deactivation protocol was used to measure IM during voltage-clamp recording with hyperpolarizing voltage steps to −65 mV (in 10-mV increments) from a holding potential of −25 mV. IM amplitude was voltage dependent and maximal current amplitude was detected at −45 mV. The deactivation time constant of IM was voltage dependent and became shorter at more negative voltages. The IM/KCNQ antagonist XE991 (0.3–30 μM) caused a concentration-dependent reduction in IM amplitude with an IC50 of 0.71 μM. Tetraethylammonium (TEA, 0.3–10 mM) caused a concentration-dependent inhibition of IM with an IC50 of 1.56 mM. In current-clamp recordings, all DA VTA neurons were spontaneously active. Analysis of evoked action potential shape indicated that XE991 (1–10 μM) reduced the fast and slow components of the spike afterhyperpolarization (AHP) without affecting the middle component of the AHP. Action potential amplitude, duration, and threshold were not affected by XE991. In addition, 10 μM XE991 significantly shortened the interspike intervals in evoked spike trains. In conclusion, IM is active near threshold in DA VTA neurons, is blocked by XE991 (10 μM) and TEA (10 mM), may contribute to the shape of the AHP, and may decrease excitability of these neurons.

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