NEUROMODULATORY MECHANISM UNDERLYING ETHANOL-INDUCED BEHAVIORAL DISINHIBITION IN DROSOPHILA
Open Access
- Author:
- Kherad Pezhouh, Maryam
- Graduate Program:
- Biology
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- None
- Committee Members:
- Andrew Paul Han, Thesis Advisor/Co-Advisor
Kyung An Han, Thesis Advisor/Co-Advisor - Keywords:
- Drosophila
Behavioral Disinhibition
Ethanol - Abstract:
- Ethanol, an active ingredient of alcohol beverages, is the most abused drug around the world and has numerous negative effects on behavior, including cognitive and motor impulsivity and addiction. The effects and underlying mechanisms of chronic ethanol exposure have been addressed in the genetically tractable Drosophila, as Ethanol affects behaviors of Drosophila and humans in a similar manner. In particular, ethanol increases disinhibited courtship between wild-type male flies (cognitive impulsivity) and the level of disinhibited courtship increases with additional ethanol exposure (behavioral sensitization). However, the cellular mechanisms underlying these phenomena are unknown. Here, we used genetic approaches to manipulate dopamine receptors and transporter to investigate their roles in the disinhibited courtship under the influence of ethanol. We also investigated the role of additional neuromodulator Amnesiac (Amn), a putative neuropeptide, since Amn is previously shown to be crucial for the ethanol’s effect on loss of motor control or sedation. Mutant flies defective in D1 receptor showed higher levels of male-male courtship compared to the wild-type flies upon exposure to ethanol. However, D2 mutant flies did not display behavioral sensitization, a type of plasticity associated with addiction. Dopamine transporter mutant fumin, which is unable to re-uptake released dopamine and thus presumably has an enhanced dopamine level, showed drastically reduced disinhibited courtship. Fumin mutant flies, on the other hand, exhibited enhanced motor impulsivity. These observations indicate the critical role of dopamine in ethanol-induced cognitive and motor impulsivity. Further characterization of the neural sites and downstream effectors that dopamine mediates ethanol-induced behavioral changes should help clarify the underlying cellular mechanisms. Various amn mutants showed inconsistent behavioral responses under chronic ethanol exposure. While amn1 mutants exhibited enhanced sensitivity to the sedative effect of ethanol and enhanced inter male courtship, other amn alleles showed normal sensitivity or reduced inter male courtship. Continued studies on the molecular and cellular characteristics of different amn alleles should help clarify discrepancies in the phenotypes and provide insights into the role of Amn in the ethanol-induced sedation and cognitive impulsivity.