Abstinence -induced withdrawal from fixed-ratio combinations of drugs and identification of amino acids in Planari

Drug abuse is a major social and medical problem and many studies have used a variety of vertebrate animal models, such as rats and monkeys, to describe and study the withdrawal from such drugs. However, many---if not most---drug abusers engage in polydrug abuse, abusing more than one drug at the same time. Yet there have been few studies that describe or quantify withdrawal from combinations of drugs. The present work will utilize the invertebrate flat worm Planaria and a mathematical tool known as 'joint-action analysis' to quantify this type of drug-drug interaction. Planaria have a primitive centralized nervous system, with mammalian-like neurotransmitter systems (e.g., dopaminergic, 5-HT, and opioid). Furthermore, Planaria have fewer complicating pharmacokinetic variables than mammals, limiting the effect that two drugs have on each other's absorption, distribution, metabolism or excretion. In preliminary work, a new metric was used to quantify dose-related withdrawal phenomena in Planaria following 1 h exposure to cocaine and the kappa-opioid agonist U-50,488H separately or together in a 1:1 fixed-ratio combination. This preliminary work will be extended to other fixed-ratio combinations of cocaine and U-50,488H and to combinations of other abused drugs. Based on recent evidence that amino acid transmitters might be implicated in drug abuse in humans, the present work will attempt to measure, using HPLC methodology, the presence of excitatory (glutamate and aspartate) or inhibitory (GABA and glycine) amino acids in Planaria. Abstinence-induced withdrawal from fixed-ratio combinations of drugs and identification of amino acids in Planaria..