Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens

The extent to which repeated administration produces tolerance to nicotine-induced increases in dopamine transmission in the nucleus accumbens was investigated in rats. In vivo microdialysis was used to sample extracellular dopamine and metabolites after a nicotine challenge (0.35 mg/kg) in (1) naive rats, (2) acutely pretreated rats (1 prior nicotine injection), and (3) chronically pretreated rats (12-15 prior daily nicotine injections, 0.35 mg/kg per injection). Nicotine increased extracellular DA and its metabolites, and these increases were not significantly altered by either acute or chronic prior exposure to the drug. The failure to find evidence of tolerance is compatible with the hypothesis that the mesolimbic dopaminergic system is a substrate for the reinforcing properties of chronically administered nicotine.     

Long-lasting effects of chronic chlorimipramine treatment of rats on exploratory activity on a hole-board, and on immobility in the forced swimming test

The study concerned the effects of acute and chronic clomipramine administration to male rats on exploratory activity in a novel environment (hole-board) and on immobility in the forced swimming test. Acute clomipramine administration did not alter either exploratory activity on a hole-board as measured 3 or 20 h after drug administration, or immobility in the forced swimming test as measured 20 h after drug administration. Approximately 20 h after the last injection of clomipramine, the rats chronically treated with the drug showed reduced exploratory activity on the hole-board. In contrast, chronic clomipramine treatment significantly increased the activity in the forced swimming test. The effects of the drug on exploratory and forced swimming activities persisted for 14 days after the cessation of clomipramine administration. These data indicate that chronic clomipramine administration exerted profound and long-lasting effects on central nervous system function. The long-lasting action of the drug on behaviour in the forced swimming test might explain the long-term beneficial effect of antidepressant drugs in counteracting behavioral depression.     

Formation of pseudodiscs in chronic recurrent Vogt-Koyanagi-Harada syndrome

We report an unusual form of chorioretinal anastomosis in a 20-year-old man with chronic recurrent Vogt-Koyanagi-Harada syndrome. Several subretinal optic disc-like lesions of subretinal fibrosis were found in the vicinity of the equator. No evidence of neovascularization or arteriovenous shunt was noted.     

Retained pacemaker leads

Increasingly, functionless pacemaker leads are being abandoned in place because they cannot be safely removed. One hundred eighty-nine intact or partially removed pacemaker leads were abandoned in situ in 152 patients between Jan. 1, 1965, and Dec. 31, 1985. The leads, sometimes several leads in a single patient, were deemed uninfected at the time of abandonment in 137 patients and contaminated with Staphylococcus epidermidis in 15 patients. All of the contaminated leads have remained clinically uninfected during follow-up. One clean lead became infected early after implantation and the patient died after an open cardiac operation to remove that lead and an adjacent abandoned lead that was adherent to the subclavian vein. No other patient has had a late complication during follow-up to 256 months (mean 47.6). Properly managed abandonment of an uninfected lead can carry a very low complication rate.     

Neuropeptide Y-like immunoreactivity in neurons of the human retina

The distribution of neuropeptide Y-like immunoreactivity (NPY-LI) was investigated in wholemounts and in transverse sections of the human retina. NPY-LI was localized to the soma and axonal processes of large ganglion cells (GCs) and to the soma and dendritic arborization of amacrine cells (ACs). NPY-LI GCs were unevenly distributed across the retina, the highest density of 875 cells/mm2 was found in the fovea centralis and the lowest density of 15 cells/mm2 in the peripheral retina. The total number of NPY-LI GCs in the retina was estimated to be about 85,000. The soma sizes of NPY-LI GCs increased from 116 microns 2 +/- 23 (s.d.) in the retinal centre to 251 microns 2 +/- 57 in the retinal periphery. The soma size of NPY-LI ACs was in the range of 40 and 50 microns 2. In transverse sections NPY-LI was seen to be localized to the optic fibre layer, to the somata of GCs, to the scleral sublamina of the inner plexiform layer (AC dendrites) and to the innermost part of the inner nuclear layer (somata of ACs). The gradients of soma sizes and retinal distribution of NPY-LI GCs were taken as an indication that they correspond to the class of large to very large GCs, previously identified in the human retina by Golgi impregnation.     

Continuous positive airway pressure in the treatment of postoperative hypoxia

The physiopathology of postoperative hypoxia has been analysed, the cause being identified in the worsening of the V/Q ratio consequent on the reduction in CFR. By increasing CFR, CPAP reduces the superimposition of Tidal Volume and Closing Volume, thus reducing dysventilated zones and thereby improving the V/Q ratio and oxyaemia. With these premises, 18 patients undergoing cholecystectomy were examined; 8 of them were treated in the postoperative period with CPAP at pre-established intervals. The results confirm its effectiveness in terms of PaO2 improvement and the need for constant administration, considering that the benefits are lost when the patient is disconnected from the mask.     

Protection of CGS 10078B against ouabain-induced arrhythmia in the cat

CGS 10078B (CGS; 1-[2,3-dihydro-1,4-(2S)-benzodioxin-2-yl]-5-[2,3-dihydro-1,4-(2R)- benzodioxin-2-yl]-3-(1R,5S)-aza-1,5-pentanediol methane sulfonate) is an agent with alpha- and beta-receptor and calcium channel blocking actions. To study its antiarrhythmic activity, cats were anesthetized with alpha-chloralose, ventilated, and given atropine and gallamine. CGS (10 or 20 mg/kg, i.v.) was infused 15 min prior to ouabain. Bolus injections of ouabain (25 micrograms/kg, i.v.) were given every 15 min until death (D). Some cats were pretreated with reserpine (R; 5 mg/kg, i.p.) 24 h prior to the experiment. In other cats 6-hydroxydopamine (6-OHDA; 20 mg/kg, i.v.) was administered 3 days prior to CGS 20 mg/kg and ouabain. Data were compared with those of Lathers [Eur. J. Pharmacol. 64: 95, 1980], i.e., with 12 cats who received only ouabain and with 11 pretreated with timolol (T; 5 mg/kg, i.v.) prior to ouabain. After CGS (10 or 20 mg/kg, i.v.), but just prior to the first dose of ouabain, the blood pressure (BP) was decreased (p less than 0.05) from control (165 +/- 6 vs. 96 +/- 7, and 136 +/- 5 vs. 90 +/- 10 mm Hg, respectively). Comparable heart rate (HR) values were also decreased (p less than 0.05) from 225 +/- 17 to 166 +/- 14 and from 193 +/- 8 to 152 +/- 6 beats/min. 11 min after T, BP and HR had decreased (p less than 0.05) from 133 +/- 6 to 103 +/- 7 mm Hg and from 134 +/- 4 to 104 +/- 6 beats/min, respectively. Ouabain did not influence these decreases in BP and HR. CGS (10 or 20 mg/kg, i.v.) increased (p less than 0.05) the time to ouabain-induced arrhythmia (AR) and D. The magnitude of the protection appeared to be similar to that afforded by T. R given prior to CGS (20 mg/kg, i.v.) also increased the time to ouabain-induced AR and D while 6-OHDA increased the time to AR. The CGS protection against ouabain-induced AR was still present in animals pretreated with R or 6-OHDA. This indicates that the antiarrhythmic affect is not dependent upon adrenergic neuronal blockade.