Functional mapping of the neuronal substrates for drug tolerance in Drosophila.
Physical dependence on alcohol and anesthetics stems from neuroadaptive changes that act to counter the effects of sedation in the brain. In Drosophila, exposure to either alcohol or solvent anesthetics have been shown to induce changes in expression of the BK-type Ca(2+)-activated K(+) channel gene slo. An increase in slo expression produces an adaptive modulation of neural activity that generates resistance to sedation and promotes drug tolerance and dependence. Increased BK channel activity counteracts the sedative effects of these drugs by reducing the neuronal refractory period and enhancing the capacity of neurons for repetitive firing. However, the brain regions or neuronal populations capable of producing inducible resistance or tolerance remain unknown. Here we map the neuronal substrates relevant for the slo-dependent modulation of drug sensitivity. Using spatially-controlled induction of slo expression we identify the mushroom bodies, the ellipsoid body and a subset of the circadian clock neurons as pivotal regions for the control of recovery from sedation.
Section of Neurobiology and Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, 1 University Station C0920, Austin, TX 78712-0248, USA.
Alfredo
A
Ghezzi
Yazan M
YM
Al-Hasan
Harish R
HR
Krishnan
Yan
Y
Wang
Nigel S
NS
Atkinson
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D019905:Benzyl Alcohol / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster; D004361:Drug Tolerance / Q000502:physiology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics
D029721:Drosophila Proteins; D006993:Hypnotics and Sedatives; D051036:Large-Conductance Calcium-Activated Potassium Channels; C494844:slo protein, Drosophila; D019905:Benzyl Alcohol