First evidence that drugs of abuse produce behavioral sensitization and cross sensitization in planarians.
Behavioral sensitization in mammals, including humans, is sensitive to factors such as administration route, testing environment, and pharmacokinetic confounds, unrelated to the drugs themselves that are difficult to eliminate. Simpler animals less susceptible to these confounding influences may be advantageous substitutes for studying sensitization. We tested this hypothesis by determining whether planarians display sensitization and cross sensitization to cocaine and glutamate. Planarian hyperactivity was quantified as the number of C-like hyperkinesias during a 1-min drug exposure. Planarians exposed initially to cocaine (or glutamate) on day 1 were challenged with cocaine (or glutamate) after 2 or 6 days of abstinence. Acute cocaine or glutamate produced concentration-related hyperactivity. Cocaine or glutamate challenge after 2 and 6 days of abstinence enhanced the hyperactivity, indicating the substances produced planarian behavioral sensitization. Cross-sensitization experiments showed that cocaine produced greater hyperactivity in planarians earlier exposed to glutamate than in glutamate-naive planarians, and vice versa. Behavioral responses were pharmacologically selective because neither scopolamine nor caffeine produced planarian behavioral sensitization despite causing hyperactivity after initial administration, and acute gamma-aminobutyric acid did not cause hyperactivity. Demonstration of pharmacologically selective behavioral sensitization in planarians suggests that these flatworms represent a sensitive in-vivo model to study cocaine behavioral sensitization and to screen potential abuse-deterrent therapeutics.
Department of Pharmaceutical Sciences, Center for Substance Abuse Research, Temple University Health Sciences Center, 3307 North Broad Street, Philadelphia, PA 19140, USA. scott.rawls@temple.edu
Scott M
SM
Rawls
Tavni
T
Patil
Ekaternia
E
Yuvasheva
Robert B
RB
Raffa
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010932:Planarians / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D019966:Substance-Related Disorders / Q000523:psychology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D018727:Muscarinic Antagonists; D002110:Caffeine; D018698:Glutamic Acid; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid; D012601:Scopolamine; D003042:Cocaine