PubMed · 8867194
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D Brooke. 1996. Why do some doctors become addicted?. https://pubmed.ncbi.nlm.nih.gov/8867194/
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Drosophila melanogaster can be used as a model organism for probing the genetic basis for alcohol sensitivity. In this paper, we describe a new device, the inebri-actometer, which measures the locomotor activity of up to 128 individual flies simultaneously. The device consists of 128 pairs of emitter/detector photodiodes connected in series through a computer interlink. A single fly is placed in each of the 128 chambers and humidified air or air containing variable amounts of ethanol vapor is pumped through the chambers. When a fly blocks the infrared signal transmitted by an emitter photodiode, the computer records one movement for that fly. We present preliminary results showing the effect of ethanol on the activity of wild-type Oregon R Drosophila. Five preliminary runs with 95% ethanol vapor revealed that this concentration induces an approximately 3- to 4-fold increase in locomotor activity which peaks at about 5 min after the addition of ethanol vapor. This is followed by a gradual decrease in activity leading to a nearly total cessation of movement after 30 min. Statistically significant dose-related activity increases were obtained for ethanol concentrations of 8, 19, 50, and 100% of maximum, assessed in two replications at each dose. Unlike the complete suppression of locomotion seen in the last 10 min of the session at maximum ethanol exposure, the initial stimulation effect at the 19% concentration was maintained across the 30-min session.
Cholecystokinin (CCK) is the most widely distributed neuropeptide in the central nervous system. One of its several functions is to modulate the release of dopamine in brain areas involved in reinforcement and reward behavior. The aim of this study was to investigate the association of CCK system genes (CCK, CCK(A) and CCK(B) receptor genes) with alcohol dependence using single nucleotide polymorphisms (SNPs) as genetic markers. A total of 257 psychiatrically interviewed Finns were genotyped for CCK (-45C>T), CCK(A) (Val365Ile) and CCK(B) (Val125Ile) receptor polymorphisms. Allele frequencies were compared between 150 unrelated healthy Finnish controls and 107 unrelated alcohol-dependent subjects (DSM-III-R criteria), who were also criminal offenders. The frequency of the CCK -45T allele was not significantly different between controls [0.07] and alcoholics [0.09]. The CCK(B) receptor polymorphism Val125Ile was also not associated with alcoholism and the Ile125 allele frequencies were 0.05 in controls vs. 0.06 in alcohol-dependent subjects. A CCK(A) receptor marker, Val365Ile, was uninformative in this Finnish dataset; all subjects were Val365/Val365 homozygous. The results suggest that CCK -45C>T and CCKBR Val125Ile polymorphisms do not have a major role in alcohol dependence in the population studied. The role of the CCK(A) the receptor in alcohol dependence remains open until additional DNA sequence variants for this gene become available.