A single high dose of cocaine induces behavioural sensitization and modifies mRNA encoding GluR1 and GAP‐43 in rats

Abstract

Neuroadaptive changes underlying repeated exposure to cocaine-induced behavioural sensitization have been related to modification in the pattern of synaptic connectivity and excitatory transmission. Remarkably, even a single exposure to abused drugs is sufficient to elicit lasting behavioural sensitization. The present study investigated whether in Sprague-Dawley rats a single, behavioural sensitizing dose of cocaine is sufficient to induce changes in the mRNA levels of growth-associated protein 43 (GAP-43), an important protein in mediating experience-dependent plasticity and synaptic reorganization, and of glutamate receptor 1 (GluR1), a subunit of AMPA glutamate receptors, a protein that is up-regulated with repeated cocaine. Single exposure to 20, but not 10 mg/kg cocaine induced locomotor sensitization to a second injection of 10 mg/kg cocaine, observed at 24 h, 48 h and 7 days. Single dose of 20 but not 10 mg/kg cocaine 48 h before scheduled death significantly enhanced GluR1 and GAP-43 mRNA expression in the nucleus accumbens (NAc), both shell and core subregions, and ventral tegmental area (VTA). No changes were found in the levels of mRNA for GluR1 and GAP-43 in the frontal cortex, caudate putamen, dentate gyrus of hippocampus and basolateral nucleus of the amygdala after the single dose of 20 mg/kg cocaine. These results further strengthen the involvement of NAc and VTA in the behavioural sensitization and suggest a role of GAP-43 in the synaptic reorganization associated to drug abuse.

Cocaine Dose and Self-Administration History, but Not Initial Cocaine Locomotor Responsiveness, Affects Sensitization to the Motivational Effects of Cocaine in Rats

“…Sensitization has been suggested to be important during the transition from recreational to compulsive cocaine use, and this idea has been argued most formally by proponents of the incentive-sensitization theory of addiction Berridge, 1993, 2001). In animals, sensitization to the locomotor-stimulating effects of drugs such as cocaine has been demonstrated for years and a great deal is known about its neurobiological mechanisms (Post, 1980;Zahniser et al, 1988;Kalivas and Duffy, 1993;Churchill et al, 1999;Grignaschi et al, 2004). However, it is not clear whether sensitization is seen in humans and nonhuman primates (Bradberry, 2007).…”

A single high dose of cocaine induces differential sensitization to specific behaviors across adolescence

“…Sensitizing drug regimens may also increase drug reward/ incentive, as they can enhance later acquisition of drug selfadministration (reviewed in Berridge 1993, 2001). Several groups have demonstrated that behavioral sensitization can be induced by a single injection of cocaine or amphetamine (Robinson et al 1982;Post et al 1987;Vanderschuren et al 1999;Grignaschi et al 2004). Studies examining stimulant-induced sensitization across adolescence have produced mixed results.…”

Drug Wanting: Behavioral Sensitization and Relapse to Drug-Seeking Behavior

“…Morphine sensitization is associated with decreased GluR2 expression in both the amygdala and the dorsal hippocampus with no changes in GluR1 levels in the hippocampus (Grignaschi et al, 2004;Sepehrizadeh et al, 2008). This could lead to enhanced levels of calcium-permeable AMPA receptors thought to underlie synaptic plasticity.…”