Chronic treatment with Tempol during acquisition or withdrawal from CPP abolishes the expression of cocaine reward and diminishes oxidative damage

Abstract

In previous studies, we reported that pretreatment with the antioxidant Tempol attenuated the development and expression of cocaine-induced psychomotor sensitization in rats and diminished cocaine-induced oxidative stress (OS) in the prefrontal cortex (PFC) and nucleus accumbens (NAc), suggesting a potential role for Tempol in interfering with cocaine-related psychomotor sensitization. The aim of the current study was to examine the role of Tempol in reward and reinforcement using the conditioned place preference (CPP) paradigm. We found that administration of Tempol during the conditioning session abolished the expression of cocaine-induced CPP. We also found that OS was significantly elevated following the establishment of CPP, and that cocaine-induced OS was significantly diminished by pretreatment with Tempol during conditioning. Furthermore, we found that repeated, but not single, administration of Tempol for seven days during withdrawal from CPP resulted in significant attenuation in the expression of CPP. Moreover, Tempol did not affect the expression of food reward. Taken together, these findings provide evidence for the involvement of Tempol in regulating cocaine rewarding properties without affecting natural rewards. Since Tempol was found to be effective in reducing OS and expression of CPP following withdrawal, it may be a potential treatment for cocaine addiction.

Role of Mitochondrial Dynamics in Cocaine’s Neurotoxicity

“…Its own degradation products, including norcocaine and norcocaine derivatives (nitroxide radical, N-hydroxy, nitrosonium, cocaine iminium, and formaldehyde), also have relatively higher oxidation potentials and result in stronger lipid peroxidation than cocaine induced itself [ 31 ]. Elevated oxidative stress has been well demonstrated in acute and chronic models of cocaine administration [ 32 , 33 ]. On the other hand, cocaine suppresses the expression and abolishes the activity of endogenous antioxidant enzymes and non-enzymatic antioxidants.…”

Dual‐specificity phosphatase 15 (DUSP15) in the nucleus accumbens is a novel negative regulator of morphine‐associated contextual memory

“…The NAc projects to motor areas such as the ventral pallidum, which externalizes these abnormally enhanced memories into addiction-related behaviours, such as compulsive drug-seeking behaviour. 8 Furthermore, the pharmacological manipulation of the NAc markedly affects the acquisition and expression of conditioned responses, 9,10 indicating that the NAc has a critical role in cue-reward learning.…”

The Role of Oxidative Stress in Cocaine Addiction

“…Recently, we studied the effect of Tempol on cocaine conditioned reward using the conditioned place preference (CPP) paradigm (Box 1). We demonstrated that injection of Tempol together with cocaine during acquisition of CPP attenuated the expression of CPP measured one day following conditioning 36 . We found that OS was significantly elevated following the establishment of CPP, and that cocaine-induced OS was significantly diminished by pretreatment with Tempol during conditioning.…”