Sex differences in ethanol-induced dopamine release in nucleus accumbens and in ethanol consumption in rats.

In vivo microdialysis was used to examine changes in nucleus accumbens and striatal dopamine, dihydrophenylacetic acid (DOPAC), and homovanillic acid (HVA) following acute administration of ethanol (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) in male and female Long-Evans rats. Following dialysis, rats were trained to bar-press for oral ethanol reinforcement. In nucleus accumbens, females showed significant increases in extracellular dopamine following 0.25 or 0.5 g/kg ethanol, but did not show significant increases over baseline at the higher doses. Males showed slight increases in dopamine at the lower doses and decreased dopamine at 2.0 g/kg. In striatum, both sexes showed increased dopamine at the lower doses and decreased dopamine at 2.0 g/kg. There were slight increases in nucleus accumbens DOPAC and HVA at some doses in both sexes, but no changes in striatal metabolite levels. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. The pattern of both greater ethanol-induced nucleus accumbens dopamine release and greater ethanol consumption in females supports the hypothesis that ethanol reward is mediated, at least in part, by the mesolimbic dopamine system.

Prenatal ethanol exposure alters ethanol-induced dopamine release in nucleus accumbens and striatum in male and female rats.

Using in vivo microdialysis, ethanol-induced dopamine release in nucleus accumbens and striatum was examined in adult male and female Long-Evans rats exposed prenatally to ethanol and in controls. Following dialysis, ethanol intake was measured in an operant paradigm. Control rats showed increased dopamine release in nucleus accumbens and striatum in response to 0.5 g/kg ethanol, but not to 1.0 g/kg. Fetal ethanol-exposed rats showed no dopamine response at 0.5 g/kg. At 1.0 g/kg, fetal ethanol-exposed males showed increased dopamine release in both structures. Prenatally exposed females showed no change in accumbens, and decreased release in striatum. Fetal ethanol exposure did not significantly influence ethanol intake. The findings suggest that prenatal ethanol exposure influences subsequent neurochemical responses to ethanol; however, how these neurochemical measures are related to ethanol intake could not be determined in the present study. Data are discussed in terms of sex-specific shifts in the dose-response function for ethanol-induced dopamine release resulting from prenatal ethanol exposure.

A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty.

OBJECTIVE: To evaluate the efficacy of continuous passive motion (CPM) in the postoperative management of patients undergoing total knee arthroplasty. DESIGN: A randomized controlled single-blind trial of CPM plus standardized rehabilitation vs standard rehabilitation alone. SETTING: A referral hospital for arthritis and musculoskeletal care. PATIENTS: Consecutive patients with end-stage osteoarthritis or rheumatoid arthritis undergoing primary total knee arthroplasty who had at least 90 degrees of passive knee flexion. One hundred fifty-four patients were eligible and 102 patients agreed to participate and were randomized. Ninety-three patients completed the study protocol. INTERVENTION: Continuous passive motion machines programmed for rate and specified arc of motion within 24 hours of surgery with range increased daily as tolerated with standardized rehabilitation program compared with standardized rehabilitation program alone. MAIN OUTCOME MEASURES: Primary outcomes were pain, active and passive knee range of motion, swelling (or circumference), quadriceps strength at postoperative day 7, as well as complications, length of stay, and active and passive range of motion and function at 6 weeks. RESULTS: Use of CPM increased active flexion and decreased swelling and the need for manipulations but did not significantly affect pain, active and passive extension, quadriceps strength, or length of hospital stay. At 6 weeks there were no differences between the two groups in either range of motion or function. In this series, use of CPM resulted in a net savings of $6764 over conventional rehabilitation in achieving these results. CONCLUSION: For the average patient undergoing total knee arthroplasty, CPM is more effective in improving range of motion, decreasing swelling, and reducing the need for manipulation than is conventional therapy and lowers cost.

Neurochemical predisposition to self-administer morphine in rats.

Using in vivo microdialysis, this study attempted to determine whether a neurochemical predisposition to self-administer morphine could be identified. Extracellular levels of dopamine and its metabolites were measured bilaterally in the mesocorticolimbic and nigrostriatal systems of naive rats that were subsequently trained to self-administer morphine intravenously. There were several significant relationships between dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and rates of morphine self-administration during both acquisition and asymptotic phases of testing. DOPAC and HVA levels in the striatum were inversely correlated with self-administration rates during the asymptotic phase whereas hemispheric asymmetries in striatal metabolite levels were inversely correlated with self-administration during the acquisition phase. DOPAC and HVA levels in in the right but not in the left side of the medial prefrontal cortex were positively correlated with self-administration rates during the acquisition phase; right/left asymmetries in cortical metabolite levels were also correlated with acquisition rates. There were no significant relationships between neurochemical indices and rates of bar-pressing for water. These results suggest that the normal variability in drug seeking behavior is at least in part attributable to individual differences in the organization and activity of brain dopamine systems. Furthermore, different mechanisms appear to be responsible for the initiation and maintenance of morphine intake: DA release in the nucleus accumbens appears to be a critical component of both mechanisms; DA release in the striatum appears to modulate maintenance and, in relationship to striatal lateralization, modulate initiation; DA release in the right but not in the left medial prefrontal cortex appears to be an important predictor of initiation.

Effects and aftereffects of ibogaine on morphine self-administration in rats.

Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addition to opiate and stimulant drugs. As a preclinical test of this claim, the present study sought to determine if ibogaine would reduce the intravenous self-administration of morphine in rats. Ibogaine dose dependently (2.5-80 mg/kg) decreased morphine intake in the hour after ibogaine treatment (acute effect) and, to a lesser extent, a day later (aftereffect); while the acute effect could be attributed to abnormal motor behavior (whole body tremors), the aftereffect occurred at a time when ibogaine should have been entirely eliminated from the body and when there was no obvious indication of ibogaine exposure. In some rats, there was a persistent decrease in morphine intake for several days or weeks after a single injection of ibogaine; other rats began to show such persistent changes only after two or three weekly injections whereas a few rats were apparently resistant to prolonged aftereffects. Aftereffects could not be attributed to a conditioned aversion. Although ibogaine also depressed responding acutely in rats trained to bar-press for water, there was no evidence of any aftereffect a day or more later; the interaction between ibogaine and morphine reinforcement was therefore somewhat specific. Further studies are needed to characterize the nature of the ibogaine-morphine interaction as well as to determine if ibogaine also affects the self-administration of other drugs.