A comparison of testing procedures on the discriminative morphine stimulus.

The study investigated the effects of reinforcement and non-reinforcement during test sessions, and the effects of duration of generalization test sessions on the generalization of a morphine-induced discriminative stimulus. Rats were trained to discriminate 3 mg/kg morphine from saline in a two-lever drug discrimination task and were then tested for generalization of 0, 1, 2, 3, 4, and 5 mg/kg morphine with the training drug under both reinforced and non-reinforced contingencies during 4-min test periods. The percentage of drug-appropriate responses and response rates were recorded for the first 2 min and the second 2 min of each test session. A higher proportion of drug-appropriate responding occurred with an intermediate dose of morphine when reinforcement was available during test sessions. The frequency of responding was higher during the last 2 min than during the first 2 min of reinforced test sessions. The changes in response rate observed between the first 2 min and the last 2 min of the test sessions also depended on the reinforcement contingency available and the dose of morphine administered presession. The testing parameters thus altered the degree of generalization and the shape of the generalization curve of the morphine discrimination.

Efficacy of choice testing to predict chronic ingestion of drinking solutions adulterated with chemicals.

The feasibility of using a measure of palatability in a 2-bottle choice paradigm to determine detriments in fluid intake when unpalatable solutions containing drugs or chemicals were provided as a sole source of fluid was examined. Palatability measures obtained from testing various concentrations of quinine with water in a two-bottle choice paradigm were compared with intake of these same solutions when they were the sole fluid source for 20 consecutive days. Mice were observed to significantly avoid quinine solutions at concentrations as low as 0.0001 mg/ml in a choice situation while fluid intake was reduced in a forced drinking situation only at a concentration of 0.1 mg/ml. Palatability altered forced fluid intake only when quinine solutions comprised 20% or less of total intake in a choice situation. This approach was successfully employed to predict whether various concentrations of halogenated hydrocarbons could be administered in a repetitive forced drinking situation without reducing total fluid intake of mice.

Pharmacological potency of R- and S-3'-hydroxy-delta 9-tetrahydrocannabinol: additional structural requirement for cannabinoid activity.

The pharmacological potency of R- and S-3'-hydroxy-delta 9-tetrahydrocannabinol (THC) was compared to that of delta 9-THC as well as R/S-3'-OH-delta 9-THC. The S-isomer was found to be considerably more potent than the R-isomer in producing hypoactivity in mice, static-ataxia in dogs, and in generalization testing in rats trained to discriminate delta 9-THC from vehicle. S-3'-OH-delta 9-THC was more active than delta 9-THC in these tests which means that delta 9-THC may be either activated or inactivated in vivo depending upon which metabolite is formed. The difference in potency of these isomers suggests that the conformation of the side chain is critical for behavioral activity. The R and S isomers were found to be equally active in producing hypothermia in mice which is in contrast to the behavioral effects.

Stimulus generalization of schedule-induced polydipsia.

Five rats were exposed to an intradimensional discrimination by associating two tones of different frequency with the components of a multiple random-time 30-sec, extinction schedule of food presentation. After schedule-induced polydipsia developed and the intermittent schedule of food presentation established stable differential licking rates during the stimuli associated with the multiple schedule, a stimulus generalization test was conducted. When generalization testing was conducted by presenting stimuli that varied on the frequency dimension during the random-time 30-sec component of the multiple schedule, all five rats demonstrated moderately sloping symmetrical gradients. Thus, schedule-induced polydipsia can be brought under the control of stimuli other than the food pellet.

Differential effects of pimozide and clozapine on schedule-controlled and scheduled-induced behaviors after acute and chronic administration.

The present study reports the comparative effects of pimozide (PMZ; 0.1, 0.3 and 1.0 mg/kg) and clozapine (CZP; 1.0, 3.0 and 10.0 mg/kg) on fixed-interval 60-sec responding after acute and chronic administration and on the acquisition of schedule-induced drinking (SID) during a chronic dosing procedure. Both the 0.3 and the 1.0 mg/kg of PMZ groups responded significantly less than vehicle controls after acute dosing without disrupting the operant response patterns as measured by index of curvature (IOC), and these effects persisted for 38 days of treatment. Acute treatment with 3.0 and 10.0 mg/kg of CZP significantly suppressed operant response rates and disrupted the pattern of operant responding, in that the IOC was significantly lower for these subjects than for vehicle controls. The CZP-treated animals gradually developed tolerance to the drug effects and were performing at vehicle control levels after Day 7 of treatment. SID was assessed from Day 19 through Day 38 of neuroleptic treatment. PMZ suppressed the acquisition of SID. Animals treated with 1.0 and 0.3 mg/kg of PMZ consumed less water than controls and did not develop the postpellet drinking pattern characteristic of SID. Both the vehicle and 0.1 mg/kg of PMZ groups increased the amount of water they consumed across the 10 blocks of sessions. A dose-related suppression of SID also was noted for CZP-treated rats. Vehicle controls and three of the subjects treated with 10.0 mg/kg of CZP acquired the SID behavior. These animals gradually increased the amount of water they consumed across sessions and drank in a temporal pattern consistent with SID.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavioral toxicity of chloral in mice: an approach to evaluation.

The potential for behavioral toxicity of the water contaminant chloral (CHL) was ascertained from acute, 14 day and 90 days of exposure in adult mice and perinatal exposure. Acute motor incoordination produced by CHL occurred 5 min after gavage and persisted for about 2 hr. The ED50 for acute CHL effects was 84.2 mg/kg, a value less than 1/10th of the acute LD50. Exposure for 14 days to either 14.4 or 144.0 mg/kg/day of CHL by gavage did not produce any deleterious effects on body weight, behavioral observations, locomotor activity, motor coordination or swimming endurance which were measured 24-48 hr after exposure was terminated. Subchronic, 90 day exposure to 0.70 or 0.07 mg/ml CHL in drinking water (15.7 and 159.8 mg/kg/day) did not affect the palatibility of drinking water since total fluid intakes were not reduced. Mice exposed to these doses of CHL did not gain weight as rapidly as control mice. Exposure to 159.8 mg/kg/day produced a decrease in body temperature after 45 days of exposure and a second temperature measurement indicated that mice exposed to both 15.7 and 159.8 mg/kg/day were hypothermic on day 91. Mice were also evaluated on various behavioral tests and none of these measures were altered by 90 days of CHL exposure. Mice perinatally exposed to 21.3 and 204.8 mg/kg/day CHL in drinking water had normal body weights, normal development of neurobehavioral reflexes and normal motor coordination. The retention of passive avoidance learning was reduced on both the 1 hr and 24 hr retention tests for mice exposed to the higher CHL concentration. CHL did not produce motor incoordination at relatively low doses following a single acute exposure. Repetitive exposure to CHL at levels of about 1/10th and 1/100th the acute LD50 for 14 or 90 days did not produce delayed or persistent behavioral changes. Non-specific effects on body temperature and body weight gains were observed for mice exposed for 90 days. There is little evidence that exposure to CHL is likely to result in delayed or persistent behavioral toxicity to adults exposed to contaminated drinking water supplies while CHL during the prenatal and early postnatal period at levels as high as 204.8 mg/kg/day can result in detrimental behavioral effects.

The BRENDA model: a psychosocial addiction model to identify and treat alcohol disorders in elders.

Studies have shown that up to 10% of the elderly drink daily and as much as 4% have alcoholism. Although many elders visit a primary care provider, the problem frequently is overlooked or misdiagnosed. We have found that primary care-based nursing is an effective treatment for older adults with alcoholism. In this article, we introduce the BRENDA model and show its effectiveness in retaining older adults in treatment. BRENDA involves biopsychosocial assessment, reporting the assessment to the patient, an empathetic approach, identified and stated patient needs, direct advice to stop or decrease alcohol consumption, and assessment of the compliance with or outcome of the direct advice. We also describe the utility of the BRENDA model for the pharmacotherapeutic treatment of addiction in late life.

Cardiomyoplasty: treatment of the failing heart using the skeletal muscle wrap.

Surgical methods of augmenting cardiac function are gaining credibility among researchers as animal and human clinical trials continue around the world. The procedures themselves may vary slightly depending upon protocol and surgeon preference, but generally involve the use of skeletal muscle such as the latissimus dorsi. The muscle may be wrapped around the heart or the aorta, or fashioned into a separate pumping chamber. The muscle is then stimulated with specialized burst pacing, the resultant contractions providing circulatory support. This article describes preoperative, intraoperative, postoperative, and follow-up patient and family care for those undergoing skeletal muscle wrap procedures. If trials continue to produce positive results, these interventions may become an important bridge to transplant. Moreover, with the scarcity of donor hearts, the implications for skeletal muscle wrapping as a long-term alternative to transplant are promising.