Abstract
Meth- and other amphetamines currently present major drug-abuse concerns. However, the demonstration and study of abuse-related behaviors expressed in animal models is expensive and time-consuming. We previously reported a novel model of conditioned place preference (CPP), which is a standard tool in abuse research, in invertebrates (planarians). In the present study, planarians were tested for light/dark preference, then exposed for 5 min to either d-amphetamine or vehicle (water) in light and then re-tested for place preference (light vs dark). The planarians’ natural strong preference for dark (15 of 16) was significantly altered by amphetamine experience, such that 12 of 16 preferred the unnatural, but amphetamine-associated, light side. These results extend the demonstration of CPP to this invertebrate species and provide further evidence in support of this model to testing/screening amphetamine-like and possibly other drugs of abuse.
Highlights
As a class, amphetamine psychostimulants have value in a number of therapeutic applications
We previously reported a novel model of conditioned place preference (CPP), which is a standard tool in abuse research, in invertebrates
Microinjections of amphetamine into nucleus accumbens establishes a CPP, and the effect is attenuated by lesions produced by 6-OHDA (6-hydroxydopamine) [29], or by microinjections into the n. accumbens of α-flupenthixol or reserpine [32], which suggests an involvement of the mesolimbic dopamine pathway in this phenomenon
Summary
Amphetamine psychostimulants have value in a number of therapeutic applications (e.g., for narcolepsy or ADHD (attention-deficit hyperactivity disorder) [1,2,3] They have potential for abuse [4], with negative health consequences [5]. The acquisition of amphetamine CPP is attenuated by the selective antagonism of the dopamine D1 [33,34] and the D2 [29,33] receptor or dual antagonism of both subtypes [35] This plus additional evidence suggests that both of dopamine receptor types are involved when dopamine is released by amphetamine during establishment of CPP [36]. Null-mutant orphan G protein-coupled receptor 37 (which colocalizes with the dopamine transporter DAT) knockout mice (GPR37-KO) do not respond to the incentive properties in CPP tests [37]
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