Drug-sensitive reward in crayfish: An invertebrate model system for the study of SEEKING, reward, addiction, and withdrawal

Abstract

In mammals, rewarding properties of drugs depend on their capacity to activate appetitive motivational states. With the underlying mechanisms strongly conserved in evolution, invertebrates have recently emerged as a powerful new model in addiction research. In crayfish natural reward has proven surprisingly sensitive to human drugs of abuse, opening an unlikely avenue of research into the basic biological mechanisms of drug addiction. In a series of studies we first examined the presence of natural reward systems in crayfish, then characterized its sensitivity to a wide range of human drugs of abuse. A conditioned place preference (CPP) paradigm was used to demonstrate that crayfish seek out those environments that had previously been paired with the psychostimulants cocaine and amphetamine, and the opioid morphine. The administration of amphetamine exerted its effects at a number of sites, including the stimulation of circuits for active exploratory behaviors (i.e., SEEKING). A further study examined morphineinduced reward, extinction and reinstatement in crayfish. Repeated intra-circulatory infusions of morphine served as a reward when paired with distinct visual or tactile cues. Morphine-induced CPP was extinguished after repeated saline injections. Following this extinction phase, morphineexperienced crayfish were once again challenged with the drug. The priming injections of morphine reinstated CPP at all tested doses, suggesting that morphine-induced CPP is unrelenting. In an exploration of drug-associated behavioral sensitization in crayfish we concurrently mapped measures of locomotion and rewarding properties of morphine. Single and repeated intra-✩ Studies reported in this paper were supported by a grant to R.H. and J.P. (NIH/NIDA 1R21DA016435-01A1) and by the help of Hope for Depression Research Foundation to J.P.

Morphine addiction in ants: a new model for self-administration and neurochemical analysis

“…An analogous response has been observed in mammals, where the release of DA into the mammalian brain directly increases rewardseeking behavior (Roitman et al, 2004;Wise, 1997). Our findings, however, seem to be in contrast to the accepted role of OA and 5-HT in invertebrate reward Barron et al, 2010;Huber et al, 2011) as neither was influenced by opioid treatment (Fig. 4B,C).…”

“…Thus, this study establishes ants as the first non-mammalian model of opioid self-administration and addiction that is truly analogous to mammals. It is well established that the phenomenon of seeking is expressed in an increased number of visits to feeders containing drugs of abuse (Huber et al, 2011;Nathaniel et al, 2010;Carrillo et al, 2008;Wise, 1997). This was first seen within our morphine-exposed ants during the sucrose-fading procedure.…”

“…4B,C). However, all previous studies investigating invertebrate reward circuitry have utilized sucrose as part of the rewarding stimuli to elicit a robust behavioral and neurochemical response Barron et al, 2010;Huber et al, 2011), not pure morphine. As all of our experimental conditions included exposure to sucrose, we cannot determine whether sucrose exposure influenced baseline DA, OA or 5-HT titer.…”

“…Cocaine can modulate bees' responses to natural floral rewards (Barron et al, 2009), while amphetamine, cocaine and morphine modulate locomotor activity in crayfish (Nathaniel et al, 2009;Huber et al, 2011). The presence of drug-seeking behavior in crayfish, honeybees and Drosophila also indicates that addiction is evolutionarily ancient (Barron et al, 2009;Nathaniel et al, 2010).…”

Reflections on the neuroscientific legacy of Jaak Panksepp (1943–2017)

“…In this sense, I believe many emotion theorists, particularly in the social constructionist school, did not fully appreciate how the SEEKING system was conceptualized as a "special class of one" in Panksepp's system of the seven emotional primes, and that it had to be the evolutionarily precedent or "master" system, a supposition recently gaining impressive validation by empirical work on dopamine in crayfish (Huber, Panksepp, Nathaniel, Alcaro, & Panksepp, 2011). In social constructional theories of emotion, the notion of "core affect" (i.e.…”