Methamphetamine self-administration in a runway model of drug-seeking behavior in male rats

Abstract

Cocaine administration has been shown to produce immediate positive (rewarding) and subsequent negative (anxiogenic) effects in humans and animals. These dual and opposing affective responses have been more difficult to demonstrate with administration of methamphetamine (meth). While animal studies have reliably demonstrated the positive reinforcing effects of the drug, reports of negative aftereffects following acute exposure have been few in number and contradictory in nature. The current research was devised to assess the effects of acute meth using a runway model of self-administration that is uniquely sensitive to both the positive and negative effects of a drug reinforcer in the same animal on the same trial. Male rats were allowed to traverse a straight alley once a day for 16 consecutive days/trials where entry into the goal box resulted in a single IV injection of meth (0.25, 0.5 or 1.0 mg/kg/inj.). The chosen doses were confirmed to be psychoactive as they produced dose-dependent increases in motoric/locomotor activation in these same subjects. The results demonstrated a U-shaped dose-response curve for the reinforcing effects of meth in that the intermediate dose group (0.5 mg/kg) produced the strongest approach behavior in the runway. Unlike other psychomotor stimulants, like cocaine, animals running for IV meth exhibited no evidence of any significant approach-avoidance behaviors reflective of the drug's negative anxiogenic effects. These results suggest that the abuse potential for meth is likely higher than for other shorter-acting psychomotor stimulants and reaffirms the utility of the runway procedure as a screen for a substance's abuse potential.

Glucagon-Like Peptide-1 Receptor Agonist Treatment Does Not Reduce Abuse-Related Effects of Opioid Drugs

“…Some authors argue that, at least in the acquisition of drug taking stage, opioids produce an almost pure euphoric (approach) response in humans and rodents, while cocaine produce mixed euphoric/aversive (approach/avoidance) effects (Badiani et al, 2011). However, this difference between cocaine and heroin in approach/avoidance behavior is most likely pharmacokinetic, with the shorter-acting cocaine producing euphoric and aversive (“crash”) effects in closer temporal proximity relative to heroin, D-amphetamine, or methamphetamine (Ettenberg, 1990, 2004, 2009; Akhiary et al, 2018). Mixed appetitive/aversive effects can be observed for all major classes of abused drugs including opioids, in humans and laboratory animals (Angst et al, 2012; Verendeev and Riley, 2013).…”