Four experiments examined the effect of naloxone pretreatment on the expression and extinction of ethanol-induced conditioned place preference (experiments 1, 2, 4) or conditioned place aversion (experiments 1, 3). DBA/2 J mice received four pairings of a distinctive tactile (floor) stimulus (CS) with injection of ethanol (2 g/kg) given either immediately before or after 5-min exposure to the CS. A different stimulus was paired with injection of saline. Pre-CS injection of ethanol produced conditioned place preference, whereas post-CS injection of ethanol produced conditioned place aversion. Both behaviors extinguished partially during repeated choice testing after vehicle injection. Naloxone (10 mg/kg) had little effect on the initial expression of conditioned place preference, but facilitated its extinction. Moreover, repeated naloxone testing resulted in the expression of a weak conditioned place aversion to the CS that initially elicited a place preference. In contrast, naloxone (1.5 or 10 mg/kg) enhanced expression of conditioned place aversion, thereby increasing its resistance to extinction. A control experiment (experiment 4) indicated that repeated testing with a different aversive drug, lithium chloride, did not affect rate of extinction or produce an aversion to the CS previously paired with ethanol. These findings do not support the suggestion that naloxone facilitates the general processes that underlie extinction of associative learning. Also, these data are not readily explained by the conditioning of place aversion at the time of testing. Rather, naloxone's effects appear to reflect a selective influence on maintenance of ethanol's conditioned rewarding effect, an effect that may be mediated by release of endogenous opioids. Overall, these findings encourage further consideration of the use of opiate antagonists in the treatment of alcoholism.

Previous studies have shown that ethanol produces conditioned place preference (CPP) in mice when injections are given immediately before exposure to the conditioned stimulus (CS). Paradoxically, however, injection of ethanol immediately after the CS produces conditioned place aversion (CPA). Four experiments were conducted to characterize the parametric boundaries of CPA produced by post-CS ethanol exposure. Experiment 1 showed that CPA is positively related to ethanol dose, with significant CPA at 2 and 4 g / kg, but not at 1 g / kg. Experiment 2 revealed an inverse relationship between CPA and trial duration, i.e. significant CPA occurred when the trial duration was 5, 15 or 30 min, but not when it was 60 or 90 min. Experiment 3 indicated that ethanol pre-exposure (eight daily injections) significantly reduced subsequent development of CPA. Finally, experiment 4 showed that repeated exposure to the CS alone (six 30 min exposures to each CS) after CS-ethanol pairings produced complete extinction of CPA. The same extinction procedure also completely eliminated CPP induced by pre-CS injections of ethanol. Overall, these studies demonstrate that CPA induced by post-CS ethanol injection is influenced by many of the same variables that affect CPP produced by pre-CS ethanol injection in mice. However, these findings do not resolve the issue of whether the 'before-versus-after' effect in ethanol place conditioning is better explained by assuming ethanol produces only rewarding effects or by assuming that ethanol produces both rewarding and aversive effects.

Short-term selective breeding created mouse lines divergent for ethanol drinking (high drinking short-term selected line [STDRHI], low drinking [STDRLO]) or ethanol-induced conditioned taste aversion (CTA; high [HTA], low [LTA]). Compared with STDRLO, STDRHI mice consumed more saccharin and less quinine, exhibited greater ethanol-induced conditioned place preference (CPP), and showed reduced ethanol stimulation and sensitization under some conditions; a line difference in ethanol-induced CTA was not consistently found. Compared with LTA, HTA mice consumed less ethanol but were similar in saccharin consumption, sensitivity to ethanol-induced CPP, and ethanol-induced locomotor stimulation and sensitization. These data suggest that ethanol drinking is genetically associated with several reward-and aversion-related traits. The interpretation of ethanol-induced CTA as more genetically distinct must be tempered by the inability to test the CTA lines beyond Selection Generation 2.

The authors surveyed 38 textbooks of abnormal psychology and found 673 pictures of the inner experience of mental disorder. Textbook authors use these pictures to demonstrate diagnostic features of individuals and groups, to make a connection between mental disorder and artistic talent, and to suggest what it is like to experience mental disorder. To fulfill these functions, many of the pictures in the sample use the incongruities and distortions of expressionist, surrealist, and naive techniques.

Sex steroids play important roles in blood pressure regulation as well as in other physiological regulatory systems. Although estrogen replacement is thought to prevent or reduce cardiovascular disease in postmenopausal women, conflicting evidence exists as to whether or not estrogen reduces blood pressure. The main purpose of this study was to determine if estrogen administration reduces angiotensin II (Ang II)‐induced increase in blood pressure in ovariectomized (OVX) mice. Four‐week‐old CD‐1 OVX mice were purchased from Envigo Inc. (Indianapolis, IN) and placed in metabolic cages for a five‐day baseline period followed by implantation of an Alzet osmotic pump containing either vehicle or Ang II (1μg/kg/min) and either a placebo or 0.7 mg b‐estradiol (E2) pellet (Innovative Research of America, Sarasota, FL). Measurements were recorded daily in the five‐day baseline and ten‐day post‐implantation periods in three groups of mice: vehicle‐placebo (V‐P), Ang II‐placebo (Ang II‐P), and Ang II‐estrogen (Ang II‐E2) (n=4/group). Mice consumed standard chow and tap water ad libitum throughout the study. Systolic blood pressure (SBP, mmHg) was determined daily via the tail‐cuff technique (CODA, Kent Scientific, Torrington, CT). The delta SBP (baseline vs Ang II periods) was higher in Ang II‐P mice but not significantly different from the Ang II‐E2 mice: (33.1 ± 3.5 vs 24.5 ± 4.0, respectively). Additionally, these values were not significantly different from the delta SBP (30.5 ± 6.1) from intact female (IF) CD‐1 mice under the same Ang II conditions determined in a previous study (Rouch, A. el al. FASEB J, 2018, A 904.6). Using repeated‐measures ANOVA, we found significant effects of E2 on water intake (WI), urine volume (UV), and sodium excretion (UNaE) during the 10‐day post‐implantation period (no differences occurred in the baseline period). E2 appeared to prevent an Ang II‐induced increase in water WI (ml/day): (Ang II‐P vs AngII‐E2; 6.9 ± 0.5 vs 4.2 ± 0.2, p < 0.001). E2 administration resulted in lower UV (ml/day): (Ang II‐P vs Ang II‐E2; 2.6 ± 0.3 vs 1.3 ± 0.2, p<0.03). E2 administration also resulted in lower UNaE (microEq/day): (Ang II‐P vs Ang II‐E2, 199.7 ± 10.8 vs 110.5 ± 20.7, p < 0.003). We conclude that continuous E2 administration via the 0.7 mg E2 pellet affects WI, UV, and UNaE during a ten‐day Ang II infusion period in OVX CD‐1 mice. Moreover, neither the pellet‐induced E2 administration nor endogenous estrogen in IF mice affected the Ang II‐induced increase in blood pressure. Studies of longer duration with more mice/group are underway to investigate mechanistic differences due to E2.Support or Funding InformationThis project was supported by the National Institute of General Medical Sciences of National Institutes of Health through Grant Number 8P20GM103447.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.