Selective ablation of GABA neurons in the ventral tegmental area increases spontaneous locomotor activity.
Gamma-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 micro-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.
Shank
Erik J
EJ
Center for Addiction Research, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USA.
Seitz
Patricia K
PK
Bubar
Marcy J
MJ
Stutz
Sonja J
SJ
Cunningham
Kathryn A
KA
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000009:adverse effects; D018847:Opioid Peptides / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1 / Q000009:adverse effects; D000076985:Saporins; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009498:Neurotoxins; D018847:Opioid Peptides; D054789:Ribosome Inactivating Proteins, Type 1; C431163:dermorphin-saporin; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D000076985:Saporins; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1