Benzodiazepine inhibits anxiogenic-like response in cocaine or ethanol withdrawn planarians

Abstract

Planarians spend less time in light versus dark environments. We hypothesized that planarians withdrawn from cocaine or ethanol would spend even less time in the light than drug-naïve planarians and that a benzodiazepine would inhibit this response. Planarians pre-treated in cocaine or ethanol were placed at the midline of a petri dish containing spring water that was split evenly into dark and light compartments. Planarians withdrawn from cocaine (1, 10, 100 µM) or ethanol (0.01 %) spent less time in the light compartment than water controls; however, this withdrawal response to cocaine (100 µM) or ethanol (0.01 %) was abolished by clorazepate (0–100 µM). These data suggest that planarians, similar to rodents, display benzodiazepine-sensitive, anxiogenic-like responses during cocaine or alcohol withdrawal.

PLDT (planarian light/dark test): an invertebrate assay to quantify defensive responding and study anxiety-like effects

“…Negative phototaxis is reduced ( i.e ., planarians spend more time in the light compartment) following conditioning sessions in which an addictive substance is paired with the light compartment (Hutchinson et al, 2015; Tallarida et al, 2014). However, following withdrawal from cocaine or ethanol exposure, planarians display enhanced negative phototaxis ( i.e ., spend less time in the light compartment) (Nayak et al, 2016).…”

Planaria: an animal model that integrates development, regeneration and pharmacology

“…From the year 2000 to date, this group has published close to 50 peer-reviewed papers or book chapters on planarian behavioral pharmacology. Some of the specific drug-related topics that the Temple group study in their planaria-related research include cross-sensitization (Rawls et al, 2010), anxiogenic-like responses (Nayak et al, 2016), dose-related physical dependence (Raffa et al, 2007), the dependence of drug exposure duration related to the withdrawal response (Sacavage et al, 2008), and abstinence-induced withdrawal among other related effects (Raffa et al, 2008). Some drugs of abuse that were tested in their work included cocaine, nicotine, amphetamines, opioids, cannabinoids, and cathinones among others.…”

Predator odor produces anxiety-like behavioral phenotype in planarians that is counteracted by fluoxetine

“…In addition, the planarian avoidant response itself (i.e., enhanced negative phototaxis) remains somewhat ambiguous in terms of biological meaning and translational significance. Light avoidance is clearly a type of defensive responding, but whether or not it also signifies anxiogenic-like behavior is unclear, although it is notable that negative phototaxis displays bidirectional expression as it is reduced by anxiolytic drugs and enhanced under known anxiogenic conditions (i.e., abstinence from chronic exposure to drugs of abuse and GABA receptor antagonism) (Zewde et al, 2018;Nayak et al, 2016). The planarian assays described here are also limited in phenotypic scope compared to mammalian models, wherein predator odor paradigms are often combined with additional stressors, such as social isolation and defeat, to produce a broader, and more robust, phenotype that better mimics PTSD in humans (Zoladz et al, 2008).…”

“…cocaine, ethanol, sucrose) but reduced during acute exposure to anxiolytic drugs (e.g. benzodiazepines and ethanol) (Nayak et al, 2016;Ouyang et al, 2017). In assays that mimic conditioned place preference (CPP) in rodents, negative phototaxis is reduced after a conditioning phase in which worms are exposed to addictive substances (e.g.…”