Selective ablation of GABA neurons in the ventral tegmental area increases spontaneous locomotor activity.

γ-aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA) provide innervation to cortical and subcortical regions of the brain. To solidify the importance of these VTA GABA neurons in behavioral function, we employed the neurotoxin dermorphin-saporin (DS) to selectively lesion VTA GABA neurons prior to assessing spontaneous motor activity. Rats were bilaterally microinfused with DS (1.0 or 2.0 pmol/200 nl/side) or blank-saporin control (BS, 200 nl/side) into the VTA. Seven days later, DS-treated rats exhibited significantly elevated motility in comparison with BS-treated rats; this elevated motility normalized by Day 14 following pretreatment with 1.0 pmol of DS but was sustained on Day 14 after pretreatment with 2.0 pmol of DS. A selective loss of VTA GABA neurons on Day 14 was demonstrated through reduced expression of mRNA for glutamic acid decarboxylase-67 and μ-opioid receptor, but not tyrosine hydroxylase (a dopamine neuron marker), in the VTA. Thus, a dose- and time-related selective loss of VTA GABA neurons was accomplished using this novel neurotoxin. This loss of GABA VTA neurons was associated with hypermotility, further supporting their important regulatory role in the generation of behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporary inactivation of ventral tegmental area neurons with either muscimol or baclofen reversibly disrupts maternal behavior in rats through different underlying mechanisms.

The purpose of this study was to examine the effects of inactivation of ventral tegmental area (VTA) projection neurons, while sparing fibers of passage, on maternal behavior in rats. Because VTA neurons contain GABA-A and GABA-B receptors, the effects of muscimol or baclofen were studied. Although bilateral injections of either drug into the VTA disrupted maternal behavior, it is likely that they did so through different underlying mechanisms. Muscimol disrupted both retrieval of pups and nursing behavior, while causing stereotyped motor activity. Baclofen disrupted retrieval behavior without affecting nursing behavior, and control injections of baclofen into the region dorsal to VTA were ineffective. The effects of VTA baclofen on maternal behavior are similar to the effects of interference with mesolimbic dopamine (DA) function. The case is made that muscimol probably caused a hyperexcitation of VTA DA neurons through a process of disinhibition. In contrast, baclofen may have depressed the activity of all VTA projection neurons, including VTA DA neurons. Baclofen is a promising tool to explore whether medial preoptic area neurons interact with VTA neurons to control active maternal responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ventral tegmental area dopamine neurons mediate the shock sensitization of acoustic startle: A potential site of action for benzodiazepine anxiolytics.

Dopamine (DA)-containing neurons in the ventral tegmental area (VTA) are thought to play an important role in fear motivation. The primary objective of the present study was to determine the connection between DA D?, gamma aminobutyric acid (GABA)A, and benzodiazepine receptors in the VTA and footshock-associated emotionality. Microinfusion of the DA D? receptor agonist quinpirole, the GABAA receptor agonist muscimol, and the benzodiazepine receptor agonist flurazepam into the VTA was observed to suppress the shock enhancement of acoustic startle amplitudes. None of the drugs depressed baseline startle responding or footshock reactivity. The results indicate the involvement of VTA DA neurons in the fear-arousing properties of footshock and implicate the VTA as a possible neural site for the anxiolytic actions of benzodiazepines. (PsycINFO Database Record (c) 2010 APA, all rights reserved)