Psychopharmacology

The combination of several risk factors (sex, a prior underlying psychiatric condition, or early drug initiation) could induce the emergence of negative affect during cocaine abstinence and increase the risk of developing addiction. However, most prior preclinical studies have been centered in male rodents, traditionally excluding females from these analyses. To ascertain the behavioral and neurochemical consequences of adolescent cocaine exposure when the combination of several risk factors is present (female, early-life stress). Whole litters of Sprague–Dawley rats were exposed to maternal deprivation for 24 h on postnatal day (PND) 9. Cocaine was administered in adolescence (15 mg/kg/day, i.p., PND 33–39). Negative affect was assessed by several behavioral tests (forced swim, open field, novelty-suppressed feeding, sucrose preference). Hippocampal cell fate markers were evaluated by western blot (FADD, Bax, cytochrome c) or immunohistochemistry (Ki-67; cell proliferation). Maternal deprivation is a suitable model of psychiatric vulnerability in which to study the impact of adolescent cocaine in female rats. While adolescent cocaine did not alter affective-like behavior during adolescence, a pro-depressive–like state emerged during adulthood, exclusively in rats re-exposed to cocaine during abstinence. FADD regulation by cocaine in early-life stressed female rats might contribute to certain hippocampal neuroadaptations with some significance to the observed induced negative affect. Adolescent cocaine induced persistent negative affect in female rats exposed to early-life stress, highlighting the risk of early drug initiation during adolescence for the emergence of negative reinforcement during abstinence likely driving cocaine addiction vulnerability, also in female rats.

Paroxetine is a selective and potent serotonin reuptake inhibitor and its efficacy for the treatment of depression has been proven. Under acute and subchronical treatment regimens, disturbances of the regular sleep pattern are a reported side effect of the drug. The present study was therefore performed to investigate the impact of subchronic treatment with the selective serotonin reuptake inhibitor paroxetine on the microstructure of the sleep EEG. The study especially addressed the question of subchronic effects of paroxetine medication (30 mg/day) in eight healthy male volunteers in a double blind, placebo-controlled crossover design. Conventional sleep EEG parameters and a spectral power analysis for different sleep stages after 4 weeks of treatment were computed. Additionally, the correlation of certain EEG rhythms across the night was calculated in order to detect subtle dynamical EEG alterations, not necessarily obvious when regarding conventional EEG analysis. Although we could not detect any alterations of the spectral power values in certain frequency bands either during NREM nor during REM sleep following subchronic paroxetine medication, the dynamical EEG attributes across the night revealed a significant enhancement of the correlation between certain EEG rhythms mainly during NREM sleep.

Lithium administration raises the minimum sodium requirement of the organism. Lithium treated-rats drink spontaneously a hypertonic sodium chloride solution and thereby protect themselves against the toxic effects of lithium. In the present paper it was studied whether the consumption of sodium chloride can be used as a quantitative measure of the sodium requirement. Rats given different amounts of lithium with food for about 2 months were given free access to water and a 0.46 M NaCl solution, and the 24-h intake of the latter was followed. It was found that the consumption of hypertonic sodium chloride increased with the lithium dosage and the serum lithium level. The consumption showed the following characteristics: (a) It was sufficient to prevent death from lithium poisoning. (b) When access to hypertonic sodium chloride was discontinued for 48 h, the rats lost body weight; the body weight was reestablished within 1 h when the rats again had access to sodium chloride solution. (c) When sufficient amounts of sodium were given with the food, the lithium-treated rats drank no more sodium chloride solution than did the control rats. (d) When lithium administration was discontinued, the consumption of sodium chloride solution fell within 10 days to the control level. (e) The lithium-treated rats developed polyuria, but this was not the cause of the extra intake of sodium chloride. (f) The lithium-treated rats did not drink more of the hypertonic sodium chloride solution than was necessary to cover the minimum sodium requirement. The results indicate that the intake of hypertonic sodium chloride solution can, in fact, be used as a measure of the minimum sodium requirement in lithium-treated rats.

Rationale: Previous work has shown that environmental enrichment alters amphetamine-induced locomotor activity and conditioned place preference. Objective: The present study examined the effect of environmental enrichment on amphetamine self-administration. Methods: Female and male rats were raised from 21 days of age in one of three different conditions: an enriched condition (EC) containing novel objects and social partners, a social condition (SC) containing social partners only, or an isolated conditioned (IC) without objects or social partners. Beginning at 51 days of age, rats were then tested for operant responding for a sucrose reinforcer using an incremental fixed ratio (FR) requirement across four sessions. Rats were then implanted with a chronic indwelling intravenous catheter and were allowed to self-administer amphetamine (0.03 or 0.1 mg/kg per infusion) for five FR1 sessions, followed by a progressive ratio (PR) session. Results: EC rats initially showed an increase in sucrose-reinforced responding relative to IC rats and this environment-induced difference was greater in females than in males. However, in both sexes, the environment-induced difference in sucrose-reinforced responding dissipated completely across repeated sessions. With amphetamine self-administration, both EC and SC rats earned fewer infusions than IC rats across repeated FR1 sessions using the low dose of amphetamine (0.03 mg/kg per infusion), but not using the higher dose of amphetamine (0.1 mg/kg per infusion). EC rats also earned fewer self-infusions of the low amphetamine dose on the PR session relative to IC rats. The effects of environmental enrichment on amphetamine self-administration were similar in both females and males. Conclusion: These results suggest that environmental enrichment may serve as a protective factor for reducing amphetamine self-administration.

Relapse is an important problem in substance dependence treatment. When drug users try to abstain from drug use, they often report strong temptations to use drugs. Temptation episodes have commonalities with relapse episodes, and assessment of temptation episodes may help to identify individuals at risk of relapse. This study aims to examine affect and cognition prior to and during temptation episodes by administering self-report and implicit cognitive assessments on a handheld computer (PDA) using Ecological Momentary Assessment. Heroin-dependent patients (N = 68) attending a drug detoxification unit completed up to four random assessments (RAs) per day on a PDA for 1 week. They also completed an assessment when they experienced a temptation to use drugs (temptation assessment; TA). Participants completed 1,482 assessments (353 TAs, 1,129 RAs). The rate of TAs was maximal during the first 2 days. Participants reported higher levels of negative affect, anxiety, and difficulty concentrating, and more positive explicit attitudes to drugs, at TAs compared to RAs. In addition, they exhibited elevated attentional bias to drug cues (assessed using the modified Stroop task) at TAs compared to RAs. Implicit affective associations with drug cues (assessed using the Implicit Association Test) were not different at TAs compared to RAs. Attentional bias was elevated in the 1 h prior to the entry of a temptation episode. Elevated attentional bias may be a harbinger of temptation episodes. Interventions that target cognitions prior to or during temptation episodes may reduce the probability or severity of a temptation episode.