Operant responding for a visual reinforcer in rats is enhanced by noncontingent nicotine: implications for nicotine self-administration and reinforcement

Rationale Current conceptualizations of drug reinforcement assume that drug-taking behavior is a consequence of the contingent, temporal relationship between the behavior and drug reward. However, stimulant drugs also potentiate the rewarding effects of other reinforcers when administered noncontingently. Objectives These studies were designed to determine whether noncontingent nicotine enhances the reinforcing properties of a nonpharmacological reinforcer and whether this direct effect facilitates operant behavior within the context of a nicotine self-administration procedure. Methods Rats self-administered nicotine or food, or received noncontingent nicotine, saline, or food either with or without a response-contingent, unconditioned reinforcing visual stimulus (VS). Results Noncontingent nicotine, whether delivered as discrete injections based on a pattern of self-administered nicotine or as a continuous infusion, increased response rates maintained by the VS. There were no significant differences in responding by animals that received contingent compared with noncontingent nicotine when a VS was available. This increase was not observed in the absence of the VS or as a consequence of noncontingent food delivery. Operant behavior was equally attenuated and reinstated by the removal and subsequent replacement of contingent and noncontingent nicotine. Nicotine supported self-administration in the absence of response-contingent, nicotine-paired stimuli; however, response rates were drastically reduced compared with nicotine self-administration with the VS. Conclusions Nicotine influences operant behavior in two ways: by acting as a primary reinforcer when it is contingent upon behavior, and by directly potentiating the reinforcing properties of other stimuli through a nonassociative mechanism. Nicotine self-administration and smoking may be largely dependent upon this later action. This work was supported by National Institute on Drug Abuse research grants, DA-10464 and DA-12655. "Principles of laboratory animal care" (NIH No. 85-23, revised 1985) were followed throughout all experiments. This research was approved by the University of Pittsburgh Institutional Animal Care and Use Committee, Assurance Number A3187-01     

Follicular carcinoma of the thyroid presenting with hematuria: a case report

A 59-year-old woman presented with hematuria in which a subsequent workup showed follicular carcinoma of the thyroid metastatic to the urinary bladder. Soft tissue metastasis from such a carcinoma is seen most commonly in the lungs and occasionally in the liver and kidneys. This case illustrates that follicular carcinoma of the thyroid may have a variable presentation, including hematuria.     

Indium-111 labeled platelet deposition following transfemoral angiography

The incidence of thromboembolitic events in patients undergoing transfemoral angiography was examined using indium-111 labeled platelets. Twenty-seven patients received approximately 300 muCi of autologous labeled platelets at least 3 hours before angiography and were scanned with a gamma camera immediately before and after angiography. All patients were free of clinically obvious complications in the 1-2 day period after angiography. Our results showed evidence of platelet deposition at 21 sites other than the puncture site in 12 (44%) patients. Most platelet deposition (54%) occurred along the region between the puncture site and the aortic bifurcation; 24% occurred at sites not traversed by the catheter. At the puncture site itself, there was substantial platelet uptake in 44% of patients. This study indicates the need for further work in determining the most suitable catheter material and in assessing the efficacy of other measures such as anticoagulant or antiplatelet therapy.     

Regulation of Gastric Corpus Tone by the Vagus Nerve in the Ferret

The pressure-volume relationship of the ferret gastric corpus was investigated to quantify the relative contributed of cholinergic and nonadrenergic, noncholinergic (NANC) mechanisms to the volume-accommodating property of this region. In splanchnectomized animals under control conditions the pressure-volume relationship of the corpus fitted a linear regression (Y = 0.30X + 0.57). Atropine decreased the magnitude of the pressure rise per unit volume, while after vagotomy this effect was reversed. The magnitude of these pressure changes in individual animals was consistent with reciprocal regulation of cholinergic and NANC pathways. Moreover, after vagotomy the shape of the pressure-volume curve was altered such that the pressure rise per unit volume was greater at the lower distending volumes. Continuous, low-frequency electrical vagal stimulation restored the pressure-volume relationship to that seen prior to vagotomy, an effect abolished by hexamethonium (25 mg/kg). Vasoactive intestinal polypeptide, on the other hand, caused a dose-related reduction in corpus pressure during the ramp increases in volume comparable to that seen during electrical stimulation but did not restore the shape of the pressure-volume curve. These data indicate that the action of the vagus may in part be permissive, with the sensitivity of local NANC pathways being modulated by a vagal cholinergic input.     

Thyrotoxic hypokalemic periodic paralysis in a white man

Thyrotoxic periodic paralysis is an uncommon complication of hyperthyroidism. Hypokalemia, with associated flaccid paralysis, is the hallmark. Oriental men are most commonly affected. We have reported a case of TPP induced by Graves' disease in a white man with hypokalemia and hypophosphatemia. He was successfully treated with radioactive ablation and short-term administration of a beta blocker. The patient has remained asymptomatic for 12 months after treatment.     

Long-term use of antecubital veins for plasma exchange. The Canadian Cooperative Multiple Sclerosis Study Group

True or sham plasma exchange was done weekly for 20 weeks in patients in two of the randomization groups in a prospective, blind clinical trial of experimental treatments for multiple sclerosis. Because patients could be randomized to receive sham plasma exchange and placebo medications, it was decided when the trial was designed that the use of fistulae, arteriovenous shunts, venous cutdowns, or other aggressive forms of venous access would not be permitted for any patient. Accordingly, patients judged to have inadequate superficial antecubital veins were ineligible for the trial. To date, only 13 (4.4%) of 294 patients considered for entry into the trial have been rejected on these grounds. In only 4 of the 93 patients undergoing exchange was it necessary to discontinue plasma exchange because of inadequate venous access. In 79.3 percent of the 1207 exchanges done in these patients, there were no problems of any kind with venous access. In 5.4 percent of these 1207 exchanges, it was necessary to terminate the procedure prematurely because of difficulties with patients' veins. Thus, the great majority of patients free of serious systemic illness (other than chronic progressive multiple sclerosis) can undergo weekly plasma exchange for up to 20 weeks using superficial antecubital veins without the need to resort to more invasive methods of venous access.     

Familial euthyroid hyperthyroxinemia secondary to pituitary and peripheral resistance to thyroid hormones

Among 18 family members, representing four generations studied, a familial form of euthyroid hyperthyroxinemia was found in 6. The increased serum total thyroxine value in all hyperthyroxinemic subjects could not be explained by abnormalities in binding proteins. Five of the six patients had a goiter, and all had increased concentrations of triiodothyronine and free thyroxine without symptoms or signs of hyperthyroidism. Basal serum levels of thyroid-stimulating hormone (thyrotropin) were normal in all six; in the four who were tested, these levels responded normally to thyrotropin-releasing hormone (TRH). The normal suppression of basal and TRH-stimulated thyrotropin increase after administration of triiodothyronine did not occur. These patients seem to have resistance of peripheral and pituitary tissues to the actions of thyroid hormones. Family studies revealed that the disorder appeared as a new sporadic mutation and was consistent with an autosomal-dominant mode of inheritance. This disorder, an important example of euthyroid hyperthyroxinemia, should not be confused with Graves' disease.