lithium-chloride and Substance-Related-Disorders

In humans, most drug use is initiated during adolescence and adolescent users are more likely to become drug-dependent than adult users. Repeated, high levels of use are required for the transition from use to addiction. Individual levels of drug use are thought to result from a balance between the pleasant or rewarding and the unpleasant or aversive properties of the drug. Repeated high levels of drug use are required for the transition from drug use to dependence. We hypothesized that diminished aversive effects of drugs of abuse during adolescence might be one reason for higher rates of use and addiction during this phase. We therefore tested adolescent and adult CD rats in single-dose cocaine conditioned taste aversion (CTA) at a range of doses (10-40 mg/kg), and examined whether various behavioral markers of addiction vulnerability were correlated to outcome in cocaine CTA. We found that adolescents are indeed less susceptible to cocaine CTA. In fact, age was the predominant predictor of CTA outcome, predominating over measures of novelty-seeking, anxiety, and stress hormone levels, which are all known to be related to drug intake in other models. Furthermore, we found that adolescent rats are also less susceptible to conditioned taste aversion to a low dose of a non-addictive substance, lithium chloride. These results suggest that one explanation for elevated drug use and addiction among adolescents is reduced aversive or use-limiting effects of the drugs. This contributes to our understanding of why adolescence is a particularly vulnerable period for development of drug abuse.

Topics: Aging; Animals; Avoidance Learning; Behavior, Animal; Cocaine; Conditioning, Psychological; Lithium Chloride; Male; Motor Activity; Rats; Rats, Sprague-Dawley; Substance-Related Disorders; Taste

Conditioned taste aversions (CTAs) are differentially induced by cocaine and morphine in the Lewis and Fisher 344 (LEW and F344, respectively) rat strains. Although the acquisition of LiCl-induced aversions has recently been reported to be comparable between the two strains, these aversions were induced by the oral consumption of LiCl, and the possibility exists that, given their different weights, that differential doses were functionally administered. To address the issue of LiCl-induced aversions in LEW and F344 rats (and to control for this possible confound), the present study assessed the ability of intraperitoneally (ip) administered LiCl to induce aversions in the two strains. Specifically, rats from both strains were given 20-min access to saccharin and injected immediately, thereafter, with 0.3, 0.6, 0.9 or 1.2 mEq/kg, 0.15 M LiCl (or its distilled water vehicle). Under these conditions, both strains acquired dose-dependent aversions that increased over repeated trials. Although there was no overall strain difference in LiCl-induced aversions, LEW rats displayed a stronger aversion at the 0.3 mEq/kg dose (on Trial 3) and acquired the aversion at this dose more rapidly than the F344 rats did (by Trial 2 vs. Trial 3). Although evident, this strain difference with LiCl does not parallel that reported with morphine (in which F344 rats are more sensitive than LEW rats) or with cocaine (in which the differences between LEW and F344 rats are larger and occur at more doses and on more trials). These cross-drug comparisons suggest that strain differences in aversion learning are drug dependent. Because drug acceptability has been reported to be a function of the balance between the reinforcing and aversive effects of various compounds, the examination of possible strain differences in aversion learning with a range of such compounds may provide insight into drug acceptability (and use) in these strains.

Topics: Animals; Cocaine; Conditioning, Psychological; Female; Lithium Chloride; Morphine; Rats; Rats, Inbred F344; Rats, Inbred Lew; Saccharin; Species Specificity; Substance-Related Disorders; Sweetening Agents; Taste

Postweaning social isolation can influence the sensitivity of rats to several effects of drugs of abuse. The present study investigated the influence of postweaning housing conditions on the sensitivity of rats to the aversive effects of a number of psychoactive agents using a conditioned taste aversion (CTA) test procedure. Development of a CTA was assessed by pairing administration of the drug with the consumption of a 0.05% (weight/volume) saccharin solution in water-deprived (18 h) rats in a 20 min drinking period. Saccharin consumption was then measured in 20 min test sessions over the next 4 consecutive days. Consumption of saccharin solution was significantly reduced in both isolated and enriched rats following administration of d-amphetamine (2 mg/kg), cocaine (30 mg/kg), morphine (10 mg/kg), nicotine (1.0 mg/kg), caffeine (20 mg/kg), alcohol (1.5 g/kg), and LiCl (0.15 M, 4 ml/kg). There was no significant effect of housing conditions on the CTA induced by cocaine, nicotine, alcohol, or LiCl; however, isolation-reared rats were found to be less sensitive to the aversive effects of d-amphetamine, morphine, and caffeine in this paradigm. These results suggest that rearing rats in social isolation induces an attenuation in sensitivity to the aversive effects of some psychoactive agents.

Topics: Animals; Antimanic Agents; Avoidance Learning; Central Nervous System Depressants; Central Nervous System Stimulants; Dose-Response Relationship, Drug; Female; Housing, Animal; Lithium Chloride; Narcotics; Psychotropic Drugs; Rats; Social Isolation; Substance-Related Disorders; Taste

Administration of pilocarpine or physostigmine to rats treated with lithium chloride produced sustained limbic seizures, widespread brain damage, and increased concentrations of D-myo-inositol-1-phosphate (a metabolite of the phosphoinositides, lipids involved in membrane receptor function) in the brain. The syndrome was preventable with atropine. The physostigmine doses and concentrations of blood lithium that caused the syndrome are similar to those considered appropriate for psychiatric chemotherapy.

Topics: Animals; Atropine; Brain Chemistry; Chlorides; Drug Interactions; Humans; Inositol; Inositol Phosphates; Lithium; Lithium Chloride; Male; Parasympathomimetics; Physostigmine; Pilocarpine; Rats; Rats, Inbred Strains; Seizures; Substance-Related Disorders

The present study was performed to investigate how lithium affects locomotor stimulation induced by dependence-producing drugs such as amphetamine, ethanol and morphine. Acute lithium alone was found to suppress exploratory hyperactivity in mice without affecting basal locomotor activity, further supporting the contention that lithium has a neurolept-like behavioural profile. Acute lithium pretreatment suppressed locomotor stimulation in mice induced by all the dependence-producing drugs in a dose-dependent manner. Locomotor stimulation seen after amphetamine and ethanol appeared to be more suppressed by lithium than that seen after morphine. Taken together with the finding that lithium had no effect on apomorphine-clonidine-induced locomotor stimulation after elimination of presynaptic activity the present data suggest that the suppressive effect of lithium is mediated via presynaptic catecholaminergic mechanisms.

Topics: Amphetamine; Animals; Chlorides; Ethanol; Female; Humans; Kinetics; Lithium; Lithium Chloride; Locomotion; Mice; Substance-Related Disorders