A cembranoid from tobacco prevents the expression of nicotine-induced withdrawal behavior in planarian worms

Abstract

Using an adaptation of published behavioral protocols, we determined that acute exposure to the cholinergic compounds nicotine and carbamylcholine decreased planarian motility in a concentration-dependent manner. A tobacco cembranoid (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol (4R-cembranoid), also decreased planarian motility. Experiments in the presence of 1 μM 4R-cembranoid did increase the IC 50 for nicotine-but not carbamylcholine-induced decrease in planarian motility. When planarians were exposed for 24 h to either nicotine or carbamylcholine at concentrations near their respective IC 50 values and then transferred to plain media, nicotineexposed, but not carbamylcholine-or cembranoid-exposed worms displayed withdrawal-like distress behaviors. In experiments where planarians were pre-exposed to 100 μM nicotine for 24 h in the presence of 1 μM 4R-cembranoid, the withdrawal-like effects were significantly reduced. These results indicate that the 4R-cembranoid might have valuable applications for tobacco abuse research. This experimental approach using planarians is useful for the initial screening of compounds relevant to drug abuse and dependence.

Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians

“…Reference [24] did not specify the chemical form of (-) nicotine that they used. It is possible that the tartrate salt decreases the potency of nicotine, however, in previous work, we observed that tartrate by itself does not induce any observable behavior in planarians [4]. This is an intriguing discrepancy that warrants further investigation.…”

“…Several studies have established the presence of cholinergic systems in planarians; acetylcholine and nicotine influence the behavior of these worms [3][4][5]. Candidate nicotinic acetylcholine receptor (nAChRs) examples have been found in planarians using various techniques including in situ hybridization [6], microarray technology [7] and expression sequence tags [8].…”

Cotinine antagonizes the behavioral effects of nicotine exposure in the planarian Girardia tigrina

“…The use of these ceramic containers allowed us to minimize the amount of reagents used. Withdrawal-like behavior experiments were adapted from established protocols [5]. Planarians were placed individually in 1.5 mL microcentrifuge tubes with experimental solutions of either APW, 100 μM nicotine, 100 μM cotinine, or a combination of 100 μM nicotine/100 μM cotinine and were closed for 21-26 hours.…”

“…In planarians, nicotine displays an increase in motility at lower concentrations, a decrease in motility at higher concentrations, and an increase in planarian seizure like movements (pSLM) [10,11]. Planarians exposed to nicotine for a period of about 24 hours display a series of withdrawal-like behaviors [5]. …”

Benzodiazepine inhibits anxiogenic-like response in cocaine or ethanol withdrawn planarians

“…These flatworms utilize neurotransmitter systems, including glutamate, dopamine, serotonin, acetylcholine, and GABA (Nishimura et al, 2010) and display mammalian-like responses to drugs of abuse including abstinence-related withdrawal, behavioral sensitization, and enhanced stereotypical activity (Pagán et al, 2009; Kusayama and Watanabe, 2000; Palladini et al, 1996). A tendency to spend less time in light versus dark environments is a behavioral phenotype of planarians (Zhang et al, 2013).…”