Peroxisome proliferator-activated receptor (PPAR) agonists as promising new medications for drug addiction: preclinical evidence.

paper Cited Public

Authors: Le Foll, Bernard; Di Ciano, Patricia; Panlilio, Leigh V; Goldberg, Steven R; Ciccocioppo, Roberto
Year: 2013
Journal: Current drug targets
PMID: 23614675
DOI: 10.2174/1389450111314070006
PMCID: PMC3826450

Figure 1

Biological effects of PPARs. CB: cannabinoid receptor; 2-AG: 2-arachindonoylglycerol; AEA: anandamide; FAAH: fatty acid amide hydrolase; OEA: oleoylethanolamide; PEA: palmitoylethanolamide; PPAR: peroxisome proliferator activated receptor

Figure 2

Clofibrate prevented the acquisition of nicotine self-administration in nicotine-naïve rats. Left panel: Vehicle-treated control rats acquired nicotine self-administration and responses in the active nose-poke hole were greater than in the inactive nose-poke hole that had no consequences. Right panel: Clofibrate pre-treatment decreased the acquisition of nicotine self-administration; responses in the inactive and active nose-poke holes were the same. Taken from Panlilio et al. (2012).

Figure 3

Reinstatement of nicotine-seeking by a priming injection of nicotine after extinction in monkeys. The PPAR-α agonist WY14643 (20 or 40 mg/kg i.p.) dose-dependently reduced the reinstatement of extinguished nicotine-seeking responses. This effect of WY14643 was prevented by pretreatment with the PPAR-α antagonist MK886 (1 mg/kg i.m.). Data are presented as mean ± SEM. *Significant difference from vehicle pretreatment during a saline prime session. #Significant difference from vehicle pretreatment during a nicotine prime session. Taken from Masica et al. (2011).

Figure 4

The effect of pioglitazone on yohimbine-induced reinstatement (left panel) and cue-induced reinstatement (right panel). During training, rats consumed alcohol prior to extinction (Ext) of this response. Compared with extinction, both yohimbine (left panel) and cues predictive of alcohol (S+; right panel) induced reinstatement of alcohol-seeking. Responding for the alcohol-predictive cues (S+) was also higher than responding for a stimulus predictive of water availability (S−). Yohimbine-induced reinstatement was reduced following treatment with pioglitazone (Pio), while cue-induced reinstatement was not affected. *Significant difference from vehicle (p<0.05 for yohimbine-induced reinstatement and p<0.01 for the cue-induced reinstatement data). Data are presented as mean ± S.E.M. Taken from Stopponi et al. (2011).

#	Section	Preview
0	Animal models for studying effects of drugs of abuse	A variety of animal models are available to study the cardinal features of drug dependence (23,…
1	Animal models for studying effects of drugs of abuse — Drug discrimination	Humans abusing psychoactive drugs report characteristic subjective effects, and drug discrimination…
2	Animal models for studying effects of drugs of abuse — Operant drug self-administration	Natural rewards, such as water, food, and drugs of abuse may serve as positive reinforcers,…
3	Animal models for studying effects of drugs of abuse — Operant drug self-administration — Fixed-ratio and progressive-ratio schedules	Under a fixed-ratio schedule, a fixed number of lever-presses are necessary to obtain each injection…
4	Animal models for studying effects of drugs of abuse — Reinstatement	The main animal models of relapse are reinstatement paradigms that model the ability of re-exposure…
5	Animal models for studying effects of drugs of abuse — Sensitization	With repeated exposure to drugs of abuse, animals can show either a heightened or decreased response…
6	PPAR-α agonists and addiction	The following review of the literature investigating effects of PPAR-α agonists on animal models of…
7	PPAR-α agonists and addiction — Drug intake	When the PPAR-α agonist clofibrate was administered prior to daily sessions when rats were first…
8	PPAR-α agonists and addiction — Drug intake	Drug intake has also been studied with a two bottle choice paradigm in which animals are given…
9	PPAR-α agonists and addiction — Reinstatement	The effects of PPAR-α agonists have been tested in both the cue-induced reinstatement and…
10	PPAR-α agonists and addiction — Sensitization	Two studies have looked at the role of PPAR-α receptors in sensitization. In one study, mutant mice…
11	PPAR-γ and addiction	In a relatively recent study looking at the expression of PPAR-γ protein in circulating monocytes…
12	PPAR-γ and addiction — Intake	In one series of experiments, the effects of PPAR-γ agonists on multiple measures of alcohol…
13	PPAR-γ and addiction — Intake	results not only suggest a selective effect of PPAR-γ agonists on intake of alcohol, as opposed to…
14	PPAR-γ and addiction — Reinstatement and withdrawal	By contrast to the effects on intake, the PPAR-γ agonist pioglitazone had no effect on cue-induced…
15	PPAR-γ and addiction — Reinstatement and withdrawal	if the two drugs were combined at relatively low doses, they were able to prevent both forms of…
16	PPAR-γ and addiction — Sensitization	Repeated daily administration of methamphetamine led to development of locomotor sensitization…
17	PPAR-γ and addiction — Sensitization	In light of the ability of PPARγ to reduce glia-mediated inflammatory response in the brain and to…
18	PPARs and dopamine neurons	The endogenous PPAR-α agonists, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) can block…
19	PPARs and dopamine neurons	Indeed, PPAR-α agonists were also effective at the terminal regions in the nucleus accumbens, an…

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