Learned tolerance to ethanol-induced c-Fos expression in rats.
ABSTRACT With c-Fos immunoreactivity as a marker for neural activity, we examined whether environmental cues associated with ethanol injection influence the expression of tolerance to ethanol-induced c-Fos activation. Over 24 training days, male Long-Evans rats received ethanol injection (2.5 g/kg) in one environment and saline injection in a different environment. Relative to rats that received ethanol for the first time, ethanol-induced c-Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and the locus coeruleus (LC) was significantly reduced in rats that had received multiple prior ethanol administrations. However, tolerance was partially reversed when ethanol was given in the saline-paired, rather than the ethanol-paired, environment. Results suggest that tolerance to ethanol, as indexed by c-Fos expression in the PVN and the LC, is mediated in part by Pavlovian conditioned responses to cues that predict ethanol administration.
- SourceAvailable from: Lorraine Weise-Kelly[Show abstract] [Hide abstract]
ABSTRACT: The Pavlovian conditioning analysis of drug tolerance emphasizes that cues present at the time of drug administration become associated with drug-induced disturbances. These disturbances elicit unconditional responses that compensate for the pharmacological perturbation. The drug-compensatory responses eventually come to be elicited by drug-paired cues. These conditional compensatory responses (CCRs) mediate tolerance by counteracting the drug effect when the drug is administered in the presence of cues previously paired with the drug. If the usual predrug cues are presented in the absence the drug, the unopposed CCRs are evident as withdrawal symptoms. Recent findings elucidate intercellular and intracellular events mediating CCRs and indicate the importance of internal stimuli (pharmacological cues and interoceptive cues inherent in self-administration) to the acquisition of drug tolerance and the expression of withdrawal symptoms.Experimental and Clinical Psychopharmacology 09/2000; 8(3):276-93. · 2.55 Impact Factor
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ABSTRACT: The induction of immediate-early genes can now be considered as a tool to study neuronal activation in different brain structures. These genes, which are rapidly and transiently induced in response to diverse extracellular stimulation, coordinate alterations in gene expression underlying neuronal plasticity. Using in situ hybridization, we found that acute i.p. cocaine (20 mg/kg) injection produced a strong expression of egr-1 and c-fos genes in the nucleus accumbens, caudate-putamen, and frontal cortex in the rat. Cocaethylene is an active metabolite of cocaine that is formed when cocaine is consumed together with ethyl alcohol. Injection of cocaethylene at a dose equivalent to cocaine induced the expression of the two immediate-early genes in the same brain structures, but to a lesser extent. A high dose of ethanol increased egr-1 and c-fos expression in the frontal cortex and in the lateral part of the caudate-putamen. Since cocaine is known to potently inhibit both dopamine and serotonin transporters, whereas cocaethylene only inhibits the dopamine transporter, our results strongly suggest that the serotonergic system participates in the mode of action of cocaine in its ability to trigger immediate-early gene transcription.Annals of the New York Academy of Sciences 10/2000; 914:46-57. · 4.38 Impact Factor
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ABSTRACT: Long-term plastic changes in the brain, including those supporting memory formation, are assumed to depend on permanent functional alterations in neuronal cells that require reprogramming of gene expression. Inducible transcription factors encoded by immediate early genes such as c-fos, c-jun, jun-B and zif/268 (also known as krox-24, egr-1, TIS 8, NGFI-A or zenk) are supposed to act as messengers in coupling short-term neuronal activity with changes at the level of gene transcription. This review will summarize studies on the expression of transcription factor-encoding immediate early genes in the vertebrate brain during behavioral training. Special emphasis will be given to correlative or interventive experimental evidence indicative of a physiological significance of inducible transcription factors for processes underlying learning and memory formation.Cellular and Molecular Life Sciences CMLS 05/1999; 55(4):564-74. · 5.62 Impact Factor