The results obtained clearly demonstrate that the cEA has a role in the regulation of ethanol consumption in the limited-access procedure. However, neither lesions of the CeA nor BNSTLP prevented the intermittent ethanol vapor-induced increase in consumption. These data do not preclude some role of the cEA in the increased ethanol consumption following intermittent ethanol vapor exposure, but would suggest that other brain regions also must have a significant influence.

Background Alcohol is frequently co-abused with smoking. In humans, nicotine use can increase alcohol craving and consumption. The objectives of the current study were to assess the acute effects of nicotine on alcohol seeking and relapse at two different time points. Method Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5 – fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hr sessions. Following 10 weeks of daily 1-hr sessions, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without EtOH or water being present for 4 sessions (Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0, 0.1, 0.3, or 1.0 mg/kg) was injected s.c. immediately or 4-hr prior to PSR or relapse testing. Results Injections of nicotine immediately prior to testing reduced (5–10 responses PSR; 50–60 responses relapse), whereas injections of nicotine 4-hr prior to testing increased (up to 150 responses for PSR; up to 400 responses for relapse with 1.0 mg/kg dose) responses on the EtOH lever during PSR and relapse tests. Discussion The results of this study demonstrate that acute effects of nicotine on EtOH-seeking and relapse behaviors may be time-dependent, with the immediate effects being a result of nicotine possibly acting as a substitute for EtOH whereas, with a delay of 4-hr, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine’s metabolites (i.e., cotinine, nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors.

Glutamine synthetase (GS, E.C. 6.3.1.2) is a ubiquitous and highly compartmentalized enzyme that is critically involved in several metabolic pathways in the brain, including the glutamine-glutamate-GABA cycle and detoxification of ammonia. GS is normally localized to the cytoplasm of most astrocytes, with elevated concentrations of the enzyme being present in perivascular endfeet and in processes close to excitatory synapses. Interestingly, an increasing number of studies have indicated that the expression, distribution, or activity of brain GS is altered in several brain disorders, including Alzheimer’s disease, schizophrenia, depression, suicidality, and mesial temporal lobe epilepsy (MTLE). Although the metabolic and functional sequelae of brain GS perturbations are not fully understood, it is likely that a deficiency in brain GS will have a significant biological impact due to the critical metabolic role of the enzyme. Furthermore, it is possible that restoration of GS in astrocytes lacking the enzyme could constitute a novel and highly specific therapy for these disorders. The goals of this review are to summarize key features of mammalian GS under normal conditions, and discuss the consequences of GS deficiency in brain disorders, specifically MTLE.

Principle-The orexin system has been hypothesized to regulate drug-seeking and drug selfadministration behaviors, including ethanol (EtOH) seeking and consumption. However, studies on the effects of orexin receptor antagonists have not been conducted on robust alcohol-relapse behavior.Objectives-This study assessed the effects of the orexin-1 receptor antagonist, SB-334867, on alcohol-seeking behavior and responding for alcohol under relapse conditions. Methods-Adult alcohol-preferring (P) rats self-trained in 2-lever operant chambers to administer 15% EtOH (vol/vol) on a fixed-ratio-5 and water on a fixed-ratio-1 schedule of reinforcement. After 10 weeks, rats underwent extinction training for 7 sessions. Animals were then maintained in their home cages for 2 weeks before being tested for Pavlovian Spontaneous Recovery (PSR; a measure of alcohol seeking) for 4 sessions. Rats were then allowed a week in their home cages before being returned to the operant chamber with access to EtOH and water (relapse). Thirty minutes before the PSR and relapse test sessions, rats received 0, 10, or 20 mg/kg SB-334867.Results-Responses on the EtOH lever during the 1st PSR test session were ~70 presses/session (3-fold higher than baseline); SB-334867 did not alter responses on the EtOH lever. Under relapse conditions, P rats increased responding on the EtOH lever from 250 (at baseline) to 350 responses/ session; both doses of SD-334867 prevented this increase. Conclusions-The results of this study suggest that activation of orexin-1 receptors is not involved in intrinsically initiated EtOH seeking, but may regulate the consummatory behavior of EtOH consumption.Keywords ethanol reinforcement; alcohol seeking; Pavlovian Spontaneous Recovery; alcohol relapse Neurons that contain orexin (hypocretin) are solely located in the hypothalamus. 1 Yet, orexinpositive neurons have a dispersed and prominent innervation pattern of cortical and subcortical regions. In particular, orexin neurons innervate the mesolimbic dopamine system and other regions associated with obtainment of positive reinforcers. For example, orexin-containing neurons are activated during foraging (food seeking 2 ) and are thought to modulate satiety and Send correspondence and reprint requests to Dr.