Effects of amphetamine on conditioned place preference and locomotion in the male green tree frog, Hyla cinerea

Abstract

Neural systems mediating motivation and reward have been well described in mammalian model systems, especially with reference to reward properties of drugs of abuse. Far less is known of the neural mechanisms underlying motivation and reward in non-mammals. The behavioral procedure conditioned place preference (CPP) is often used to quantify reward properties of psychoactive drugs. The indirect dopamine agonist d-amphetamine (AMPH) is known for its properties for inducing CPP in mammals and for inducing dose-related stereotypic movements. We used the green tree frog, Hyla cinerea, to examine whether AMPH could induce both CPP and a dose response change in motor behaviors. We demonstrated that H. cinerea can show place conditioning to AMPH following 14 days of training and that AMPH can cause reversal of a strong baseline place preference. Amphetamine-treated animals (20 mg/kg b.w.) received the drug paired with the previously non-preferred context, and vehicle paired with the preferred context. Control animals received vehicle in both preferred and non-preferred contexts. Amphetamine-treated animals switched context preference following conditioning, whereas control animals did not. We also demonstrated in an open-field experiment that AMPH did not cause any noticeable changes in motor movement or behaviors across a range of doses (0, 10, 20 mg/kg b.w.). This study represents the first examination of the behavioral effects of AMPH in amphibians. These results may contribute to a better understanding of the function and pharmacology of a reward system that may mediate natural behaviors in frogs and other vertebrates.

Fig. 1

Schematic of the place-conditioning chamber, designed for tree frogs. Schematic shows the chamber with the dividing partition in place. During the test day of the conditioning experiment and for all locomotor experiments, the partition was removed.

Fig. 2

The amount of time each animal spent in the preferred and non-preferred contexts following 4 days of pre-exposure to the conditioning chamber. Frogs showed a strong baseline preference for one of the contexts (p < 0.0001).

Fig. 3

a The amount of time spent in the initial ‘preferred’ context before and after 14 days of conditioning. Frogs receiving AMPH paired with the non-preferred context showed decreased time spent in the preferred context following conditioning. Control animals did not. b The strength of conditioned preference. The change in the amount of time spent in the non-preferred side following conditioning, relative to baseline. ∗ p < 0.05, ∗∗ p < 0.01.

Fig. 4

a Number of movements made during the baseline and test conditions for vehicle- and AMPH- (10 and 20 mg/kg b.w.) treated animals. Animals moved less on test day regardless of drug treatment. ∗∗ p < 0.01. b Relative change in number of movements during the test condition relative to baseline. There were no significant differences in relative numbers of movements made across drug treatment.