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.
"Over the past several years, c-Fos immunohistochemistry has been used to identify neuronal sites activated by ethanol administration. Ethanol-induced c-Fos-like immunoreactivity (cFLI) has been identified in several forebrain regions that include the bed nucleus of the stria terminalis, the paraventricular nucleus of the thalamus and hypothalamus, the central nucleus of the amygdala, and the nucleus accumbens (Chang et al., 1995; Hitzemann and Hitzemann, 1997; Ryabinin et al., 1997; Thiele et al., 1998b; Zoeller and Fletcher, 1994). In the brainstem, ethanolinduced cFLI has been observed in regions that include the lateral parabrachial nucleus (PBN), the area postrema (AP), the locus coeruleus (LC), and the nucleus of the solitary tract (NTS) (Ryabinin et al., 1997; Thiele et al., 1996, 1997, 1998b). "
[Show abstract][Hide abstract] ABSTRACT: Background: Previous studies have used c-Fos-like immunoreactivity (cFLI) to examine the neuroanatomical location of cells that are activated in response to ethanol administration. However, the use of cFLI alone fails to reveal the phenotypical identity of cells. In the present study we used double-labeling procedures to identify the neurochemical phenotype of neurons that showed ethanol-induced cFLI in the rat brainstem.Methods: Individual groups of rats received intraperitoneal injection of ethanol (1.5 g/kg or 3.5 g/kg) or isotonic saline (23 ml/kg). To assess the specificity of cFLI induced by ethanol, we injected other rats with the drug lithium chloride (LiCl; 76 mg/kg). Two hours after injection, rats were killed and their brains were processed for immunohistochemistry.Results: Both doses of ethanol promoted cFLI in several brainstem regions, including the nucleus of the solitary tract (NTS), the locus coeruleus (LC), and the ventrolateral medulla (VLM). Although LiCl caused significant cFLI in the NTS, this drug promoted only minimal cFLI in the VLM and no significant activation in the LC. We found that a significant proportion of tyrosine hydroxylase (TH)-positive neurons coexpressed ethanol-induced cFLI in the VLM (∼75–85%), the NTS (∼65–75%), and the LC (∼30–65%). Additionally, a significant proportion of neuropeptide Y (NPY)-producing neurons in the VLM coexpressed ethanol-induced cFLI (∼60–75%). On the other hand, LiCl promoted activation of TH-positive neurons in the VLM and the NTS but failed to stimulate cFLI in TH-producing neurons in the LC or in NPY-producing neurons of the VLM.Conclusions: Neurons in the rat brainstem that show ethanol-induced c-Fos expression produce catecholamines and NPY. This research demonstrates the usefulness of double-labeling immunohistochemistry procedures for identifying the neurochemical identity of neurons that are activated after ethanol administration.
Alcoholism Clinical and Experimental Research 05/2000; 24(6):802 - 809. DOI:10.1111/j.1530-0277.2000.tb02059.x · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the molecular mechanisms that mediate the effect of learning on morphine tolerance in rats, we examined striatal c-Fos, and c-Jun protein expression, and AP-1 DNA binding. Morphine paired with a conditioned stimulus (CS) led to analgesic tolerance in the presence of the CS. Rats receiving morphine unpaired with the CS displayed significantly less tolerance than paired morphine animals. Striatal c-Fos protein levels and AP-1 DNA binding activity were increased in rats receiving paired morphine compared with rats that did not receive morphine but not in rats receiving morphine without the CS. No differences were found in c-Jun levels. These results suggest that Pavlovian conditioning may account, in part, for the molecular mechanisms associated with morphine tolerance.
[Show abstract][Hide abstract] 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. DOI:10.1007/s000180050315 · 5.81 Impact Factor
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