The role of progestins in the behavioral effects of cocaine and other drugs of abuse: human and animal research - PubMed (original) (raw)
Review
The role of progestins in the behavioral effects of cocaine and other drugs of abuse: human and animal research
Justin J Anker et al. Neurosci Biobehav Rev. 2010 Nov.
Abstract
This review summarizes findings from human and animal research investigating the influence of progesterone and its metabolites allopreganolone and pregnanolone (progestins) on the effects of cocaine and other drugs of abuse. Since a majority of these studies have used cocaine, this will be the primary focus; however, the influence of progestins on other drugs of abuse will also be discussed. Collectively, findings from these studies support a role for progestins in (1) attenuating the subjective and physiological effects of cocaine in humans, (2) blocking the reinforcing and other behavioral effects of cocaine in animal models of drug abuse, and (3) influencing behavioral responses to other drugs of abuse such as alcohol and nicotine in animals. Administration of several drugs of abuse in both human and nonhuman animals significantly increased progestin levels, and this is explained in terms of progestins acting as homeostatic regulators that decrease and normalize heightened stress and reward responses which lead to increased drug craving and relapse. The findings discussed here highlight the complexity of progestin-drug interactions, and they suggest a possible use for these agents in understanding the etiology of and developing treatments for drug abuse.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Figures
Figure 1
Plasma concentrations of EST (solid line) and PROG (dashed line) across the human and nonhuman menstrual cycle
Figure 2
Plasma concentrations of EST (solid line) and PROG (dashed line) across the rodent estrous cycle
Figure 3
Data represent the mean (± SEM) cocaine infusions self-administered each day of the LgA phase. Horizontal lines indicate the 3-day intervals during which there were significant group differences in drug deliveries (p<0.05). Panel A: * = p<0.05 block 1<blocks 3–7; block 2<blocks 5–7 in the OVX-EST group, # = p<0.05 block 1<blocks 4–7 in the SH-VEH group, and @ = p<0.05 block 1<blocks 5–7; block 2<blocks 6 and7; block 3<block 7 in the OVX-VEH group. Panel B:†= p<0.05 block 1< blocks 3–7 in the VEH group.
Figure 4
Black bars represent the mean (± SEM) responses on the cocaine-paired lever following a 10 mg/kg cocaine priming injection and white bars refer to responses on the same lever after a saline priming injection. All groups responded more on the cocaine-paired lever after a 10 mg/kg cocaine i.p. than after a saline i.p. (* = p<0.05). Significant group differences in cocaine-primed responding are represented by # (p<0.05). Panel C: †= p<0.05 VEH>ALLO in the female group.
Figure 5
Mean (± SEM) responses on the previously drug-paired lever following saline (S) or YOH (Y) priming injections during the reinstatement procedure. Asterisks indicate significantly greater responding following YOH compared to S priming injections (p<0.05). # = a significant difference in YOH compared to responding following A+Y in the female group (p<0.05), and †= a significant sex difference (females>males) in responding following the first YOH injection (p<0.05).
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