Intravenous Drug Self-administration in Mice: Practical Considerations

Abstract

Chronic intravenous drug self-administration in rodents is a useful procedure for predicting the abuse liability of novel drugs in humans, for evaluating candidate treatments for drug abuse and dependence, and for studying the biological basis of addiction. Despite the technical challenge in achieving chronic self-administration behavior in the mouse species, researchers are increasingly using genetically engineered mice to investigate the role of specific genes in abuse-related effects of drugs. This review focuses on recent technical innovations as well as theoretical considerations for comparing intravenous (i.v.) drug self-administration behavior between mouse strains, including mice with targeted mutations. Part I of the present article describes techniques for successfully conducting self-administration studies in mice, including advantages, disadvantages and possible implications of employing various experimental approaches. Part II provides a review of recent data that address how the genetic background on which mutations are expressed may influence results from gene-targeting studies.

Constitutive Knockout of Kalirin-7 Leads to Increased Rates of Cocaine Self-Administration

“…2). Previous studies have demonstrated a plateau in responses by C57BL/6 mice at 1.0 mg/kg/infusion (Thomsen and Caine, 2007), and our data concur (Supplemental Fig. 2).…”

“…The animals that were trained at the 1.0-mg/kg dose then went on to a 1-day progressive ratio task, which also demonstrated no genotypic difference in the number of infusions earned (graph not shown: Wt 6.92 6 1.4; Kal7 KO 5.49 6 1.3; results of a two-tailed t test showed t 5 0.78, df 5 51, P 5 0.44). Higher doses of cocaine per infusion were not tested, as previous studies have shown 1.0 mg/kg to be the dose at which C57/bl6 mice typically plateau (Thomsen and Caine, 2007).…”

Operant, oral alcoholic beer self-administration by C57BL/6J mice: effect of BHF177, a positive allosteric modulator of GABAB receptors

“…First is the use of freefed mice. Food restriction is a common strategy to increases rodents' operant responding in self-administration procedures (Caine et al, 1993;Elmer et al, 1986;Hayward et al, 2004;Heidbreder et al, 2007;Nguyen et al, 2005;Middaugh et al, 1999;Thomsen and Caine, 2007). However, the fact that this can alter the neurochemical pathways mediating drug-reinforcing properties is often overlooked: a 20-50% decrease in extracellular dopamine (DA) levels was observed in the nucleus accumbens (NAc) of food-restricted rats (Pothos et al, 1995).…”

Contemporary approaches to neural circuit manipulation and mapping: focus on reward and addiction

“…These behaviours are known to differentially rely on dopamine signalling [134,202,203] and predict different forms of relapse [150,204,205]. Drug self-administration studies using intravenous catheters [206] and certain impulsivity tasks [207,208] are also much more challenging to conduct in mice. Additionally, some behaviours believed to serve as particularly useful models of human relapse and addiction, including compulsive cocaine seeking in the face of punishment [209], are unexplored in mice.…”