Aerobic exercise can serve as an alternative, non-drug reinforcer in laboratory animals and has been recommended as a potential intervention for substance abusing populations. Unfortunately, relatively little empirical data have been collected that specifically address the possible protective effects of voluntary, long-term exercise on measures of drug self-administration. The purpose of the present study was to examine the effects of chronic exercise on sensitivity to the positive-reinforcing effects of cocaine in the drug self-administration procedure. Female rats were obtained at weaning and immediately divided into two groups. Sedentary rats were housed individually in standard laboratory cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed individually in modified cages equipped with a running wheel. After 6 weeks under these conditions, rats were surgically implanted with venous catheters and trained to self-administer cocaine on a fixedratio schedule of reinforcement. Once self-administration was acquired, cocaine was made available on a progressive ratio schedule and breakpoints were obtained for various doses of cocaine. Sedentary and exercising rats did not differ in the time to acquire cocaine self-administration or responding on the fixed-ratio schedule of reinforcement. However, on the progressive ratio schedule, breakpoints were significantly lower in exercising rats than sedentary rats when responding was maintained by both low (0.3 mg/kg/infusion) and high (1.0 mg/kg/infusion) doses of cocaine. In exercising rats, greater exercise output prior to catheter implantation was associated with lower breakpoints at the high dose of cocaine. These data indicate that chronic exercise decreases the positive-reinforcing effects of cocaine and support the possibility that exercise may be an effective intervention in drug abuse prevention and treatment programs.

Environmental enrichment produces functional changes in mesolimbic dopamine transmission and alters sensitivity to psychomotor stimulants. These manipulations also alter the control rate of many behaviors that are sensitive to stimulant administration, which can make comparison of drug effects between isolated and enriched subjects difficult. The purpose of this study was to examine the effects of environmental enrichment on control rates of behavior and on sensitivity to cocaine in tests of locomotor activity, drug self-administration, conditioned place preference, and toxicity. In the locomotor activity test, isolated rats exhibited greater activity after the administration of cocaine, but also had higher control rates of activity. When locomotor activity was expressed as a percentage of saline control values, enriched rats exhibited a greater increase relative to their own control than isolated rats. In the drug self-administration procedure, isolated rats had higher breakpoints on a progressive-ratio schedule of reinforcement when responding was maintained by cocaine; however, isolated rats also had higher breakpoints in saline substitution tests and higher rates of inactive lever responding. When the self-administration data were expressed as a percentage of these control values, enriched rats exhibited a greater increase in responding relative to their own control rates than isolated rats. No differences were observed between isolated and enriched rats under control conditions in the place preference and toxicity studies. In both of these procedures, enriched rats were more sensitive than isolated rats to all the doses of cocaine tested. These data emphasize the importance of considering control rates of behavior in studies examining environmental enrichment and drug sensitivity, and suggest that environmental enrichment increases sensitivity to cocaine across a range of dependent measures whether differences in control rates of behavior are taken into account.

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Repeated administration of many addictive drugs leads to a progressive increase in their locomotor effects. This increase in locomotor activity often develops concomitantly with increases in their positive-reinforcing effects, which are believed to contribute to the etiology of substance use disorders. The purpose of this study was to examine changes in sensitivity to the locomotor effects of opioids after their repeated administration and to determine the role of and receptors in mediating these effects. Separate groups of rats were treated with opioid receptor agonists and antagonists every other day for 10 days, and changes in locomotor activity were measured. Repeated administration of the agonists, morphine and buprenorphine, produced a progressive increase in locomotor activity during the treatment period, and this effect was blocked by coadministration of the opioid antagonist naltrexone. The agonist spiradoline decreased locomotor activity when administered alone and blocked the progressive increase in locomotor activity produced by morphine. The ability of spiradoline to block morphine-induced increases in locomotor activity was itself blocked by pretreatment with the antagonist nor-binaltorphimine. Repeated administration of high doses, but not low or moderate doses, of the mixed / agonists butorphanol, nalbuphine, and nalorphine produced a progressive increase in locomotor activity during the treatment period. Doses of butorphanol, nalbuphine, and nalorphine that failed to produce a progressive increase in locomotor activity when administered alone did so when subjects were pretreated with nor-binaltorphimine. These findings suggest that and receptors have functionally opposing effects on opioid-mediated locomotor activity and sensitization-related processes.Locomotor activity after psychotropic drug administration has long been of interest to behavioral pharmacologists in general and substance abuse researchers in particular. The reasons for this interest can be traced to the fact that the anatomical structures and neurotransmitter systems mediating locomotor activity overlap those that mediate positive reinforcement and reward (for review, see Wise, 1987;Tzschentke, 2001). Because of this overlap, a careful examination of locomotor activity after drug administration can shed light on the neuropharmacological basis of substance abuse and other addictive behaviors.Opioid analgesics produce a stereotypical pattern of locomotor activity that has been well characterized. After systemic administration, -opioid agonists initially produce a transient decrease in locomotor activity that gradually dissipates over the course of 60 to 120 min, which is then followed by an increase in locomotor activity lasting several hours (Babbini and Davis, 1972;Buxbaum et al., 1973). Sensitivity to both the initial decrease and the subsequent increase in locomotor activity changes after the repeated administration of opioids, such that the initial decrease becomes gradually smaller, and the subsequent increase becom...

Sensitization refers to an increase in sensitivity to a drug and is believed to play a role in the etiology of substance use disorders. The purpose of the present study was to evaluate the ability of the mixed mu/kappa agonist nalbuphine to modulate sensitization to the locomotor and positive reinforcing effects of cocaine. Rats were habituated to a locomotor activity chamber and treated with saline (1.0 ml/kg, ip), cocaine (10 mg/kg, ip), or cocaine + nalbuphine (10 mg/kg, ip) every day for 10 days. Following locomotor activity testing, rats were implanted with intravenous catheters and cocaine self-administration was examined on fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. Rats treated with cocaine exhibited a progressive increase in locomotor activity over the 10-day treatment period, and this effect was significantly reduced in rats treated with cocaine + nalbuphine. In self-administration tests, rats treated with cocaine exhibited significantly higher levels of responding at a threshold dose of cocaine (0.03 mg/kg/infusion) on both FR and PR schedules than rats treated with saline. This increase in responding at a threshold dose of cocaine was blocked completely in rats treated with cocaine + nalbuphine. These data suggest that nalbuphine attenuates the development of sensitization to the behavioral effects of cocaine.

Sensitization refers to an increase in sensitivity to the effects of a drug and is believed to play a role in the etiology of substance use disorders. Cross-sensitization has been observed between drugs from different pharmacological classes and may play a role in the escalation of drug use in polydrug-abusing populations. The purpose of this study was to examine cross-sensitization between opioids and cocaine and to determine the extent to which cross-sensitization is mediated by an opioid's selectivity for , , and ␦ receptors. Separate groups of rats were treated with opioid receptor agonists and antagonists every other day for 10 days, and the locomotor effects of cocaine were tested 8 days later. The agonists, morphine and buprenorphine, and the, produced cross-sensitization to cocaine, such that repeated administration of these drugs over a 10-day period significantly enhanced cocaine's locomotor effects when tested later. Coadministration of the opioid antagonist naltrexone prevented morphine and buprenorphine from producing cross-sensitization. Coadministration of naltrexone, but not the ␦ antagonist naltrindole, also prevented BW373U86 from producing crosssensitization. The agonist spiradoline failed to produce crosssensitization, but coadministration of spiradoline prevented morphine and buprenorphine from producing cross-sensitization. The ability of spiradoline to block cross-sensitization was itself blocked by the antagonist nor-binaltorphimine. The mixed / opioids butorphanol, nalbuphine, and nalorphine did not produce cross-sensitization under any condition examined. These data indicate that agonist activity at receptors positively modulates cross-sensitization between opioids and cocaine, whereas agonist activity at receptors negatively modulates this effect.

Several studies report that environmental enrichment enhances sensitivity to opioid receptor agonists in male rats. Very few studies have examined the effects of enrichment in female rats, and thus it is not clear whether females are similarly sensitive to these effects. Consequently, the purpose of the present study was to examine the effects of environmental enrichment on sensitivity to representative mu, kappa, and mixed-action opioids in female rats. Following a protocol established in males, females were obtained at weaning and randomly assigned to two groups immediately upon arrival: isolated rats were housed individually with no visual or tactile contact with other rats; enriched rats were housed in groups of four in large cages and given various novel objects on a regular basis. After 6 weeks under these conditions, the antinociceptive effects of mu (morphine, levorphanol), kappa (spiradoline, U69,593), and mixed-action (buprenorphine, butorphanol) opioids were examined in a warm-water, tail-withdrawal procedure. All the opioids examined produced dose-dependent increases in antinociception; however, no differences in opioid sensitivity were observed between the two groups. To determine whether these findings were consistent across behavioral endpoints, the antidiuretic effects of representative mu opioids, and the diuretic effects of representative kappa opioids, were examined in female rats reared under isolated or enriched conditions for 10 weeks. Similar to that seen in the antinociceptive experiment, no significant differences in opioid sensitivity were observed between groups. These data indicate that environmental enrichment does not alter sensitivity to the effects of opioid receptor agonists in female rats, and suggest that females may respond differently to environmental enrichment than males. Keywordsantidiuresis; antinociception; diuresis; enrichment; female; isolation; opioid; rat A large number of studies reveal that environmental manipulations during critical periods in development can influence the physical maturation of the nervous system and produce functional effects on behavior. For example, male rats reared under conditions of environmental enrichment (i.e., conditions in which rats were housed together in large groups and provided with novel objects on a regular basis) had greater cortical mass [1,2], had greater dendritic branching on cortical neurons [3,4], and performed better in learning and memory tasks [5,6] than animals reared in isolation under impoverished conditions. Interestingly, these same types of manipulations can also influence an organism's sensitivity to the neurochemical Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be ...

BackgroundCases of isolated intramedullary spinal neurocysticercosis are extremely rare. Only 25 cases have been reported before 2022. Due to its rarity, the diagnosis of spinal neurocysticercosis may be missed.Case presentationWe describe a 37-year-old female patient who developed back pain and lower extremity weakness and was found to have an intramedullary thoracic spine cystic lesion. She was taken to the operating room for resection of the lesion. Pathology revealed a larval cyst wall consistent with neurocysticercosis. The patient was started on albendazole and dexamethasone. Her exam improved post-operatively, and she was able to ambulate with minimal difficulty at the time of follow up.ConclusionThe case provides insights on the diagnosis and treatment of isolated intramedullary spinal neurocysticercosis. Review of the literature suggests that combined surgical and medical intervention results in significant improvement in the patient's neurological exam, and decreases morbidity associated with the disease. We propose a treatment paradigm for this rare manifestation of neurocysticercosis.