Neurotensin injected into the nucleus accumbens blocks the psychostimulant effects of cocaine but does not attenuate cocaine self-administration in the rat

The neuropeptide neurotensin (NT) has been shown to modulate mesolimbic dopaminergic activity. Neurotensin injected into the VTA produces motor stimulation and release of dopamine in the nucleus accumbens. In contrast, when neurotensin is administered into the nucleus accumbens, it produces neuroleptic-like effects such as attenuation of the locomotor activity elicited by psychostimulants. In the present study, the hypothesis that neurotensin injected into the nucleus accumbens might modulate the psychostimulant and reinforcing actions of cocaine was tested. In experiment one, rats were trained to self-administer cocaine intravenously on an FR5 schedule of reinforcement. Following the establishment of baseline responding, rats were implanted with bilateral cannulae in the nucleus accumbens. One week later, rats were injected into the nucleus accumbens with various doses of neurotensin (4.2, 8.4 and 16.7 μg, total doses bilaterally) immediately prior to the self-administration session. No significant effects were found with any of the doses of neurotensin tested on the self-administration of cocaine. However, in experiment 2, neurotensin at doses of 4.2 and 16.7 μg injected into the nucleus accumbens significantly reduced the locomotor activation induced by an acute injection of cocaine (15 mg/kg i.p.) and a dose of 16.7 μg attenuated the locomotor activation induced by amphetamine (0.75 mg/kg i.p.). Thus, neurotensin in the nucleus accumbens appears to specifically modulate the acute locomotor activating properties of cocaine but not cocaine self-administration. Different mechanisms by which NT interacts with dopamine in the nucleus accumbens may provide a means of selectively altering psychostimulant motor actions without affecting psychostimulant reinforcement.     

How reproducible is cutaneous electrogastrography? An in-depth evidence-based study1

AIM: To check on reproducibility of parameters of the cutaneous electrogastrogram registered at a close or a distant time span. METHODS: Twenty-two volunteers recruited by an advertisement (11 females and 11 males, median age 25 years, range: 18-35) underwent three surface electrogastrography examinations of which two were taken on consecutive days and the third one was accomplished at least 2 weeks before or after the two other sessions. The examination involved a 30-min fasted recording, followed by a 90-min postprandial registration after intake of a 394-kcal mixed solid-liquid test meal. RESULTS: Parameters of the electrogastrogram pertaining to the frequency of the gastric slow waves exhibited good to moderate reproducibility, whereas fair reproducibility characterized parameters expected to describe the power of gastric slow waves. With the exception of the difference fed minus fasted power (DeltaDP), in no instance was the medium term reproducibility any worse than the short term one. Categorical data analysis revealed that the relative time share of normogastria postprandially exhibited a better reproducibility than in the fasted period. The Cohen's kappa-value of 0.459 for the DeltaDP for the medium term reproducibility placed this parameter within the range of moderate agreement between repeat examinations. Of the two two-parameter combinations considered, the alliance of the fasted and fed normogastria performed worse than any of those parameters considered alone, whereas a combination of the DeltaDP with the fed-state normogastria revealed a kappa-value amounting to 0.510 for the medium term reproducibility. CONCLUSIONS: The feasibility of some electrogastrographic parameters to convey clinically useful information may be hampered by their fair reproducibility. Recoding of parameters of the cutaneous electrogastrogram from primary continuous to secondary categorical may help achieve a better agreement between repeat examinations.     

Effects of chelating agents on the rheological property of cervical mucus

As an ongoing effort to elucidate the mechanisms involved in the calcium-dependent fertility regulation process, the viscoelastic properties of the mucus obtained from lamb cervix and human semen, as well as their water and total protein contents after exposure to EDTA, a chelating agent, or Nonoxynol-9 (N-9), a spermicidal agent, were examined. The viscosity was measured using a Cone Plate Digital Viscometer, while the water and total protein contents were determined by the lyophilization process and the Lowry method, respectively. The significant changes in the rheological properties of mucus, such as its viscosity and the water content, upon exposure to EDTA were demonstrated. The viscosity of cervical mucus and human semen were significantly increased by EDTA treatment (as compared to the controls): lamb cervical mucus (2.9 ± 0.3 vs. 2.2 ± 0.3 cps) and human semen (5.0 ± 0.3 vs. 4.3 ± 0.3 cps), respectively. The hydration rate was decreased by EDTA treatment as compared with the control (93.6 ± 0.7 vs. 96.8 ± 0.8%). Among tested samples, the reduction in the percentage of sperm penetration through the cervical mucus was the highest in the mucus containing EDTA, which had the lowest water content (93.6 ± 0.7%), indicating that there is a positive relationship between the hydration rate of the cervical mucus and its ability to permit the penetration of spermatozoa. This result indicates that spermicidal activity exerted by high concentrations of EDTA is in part due to its effect on the rheological properties of cervical mucus or semen.     

Behavioral models in mice. implication of the alpha noradrenergic system

1. The mechanism of action of drugs might change according to the test used. Several noradrenergic drugs were tested in order to understand their implication in the mobility tests.

2. It was found that clonidine, an Alpha 2 agonist, acted differently according to the tast used. It provoked sedation in spontaneous activity test, and anti-immobility effects in the other tests.

3. Tall suspension test is able to show the double acting of clonidine.

4. Idazoxan might act either as an alpha 2 antagonist or as partial alpha 2 agonist. TST shown the unexpected partial alpha agonist effect of the molecule.

5. Forced swimming test is more specific for predicting antidepressant activity than tail suspension test which is close to a spontaneous activity model.     

Studies on the effects of Pluchea indica less root extract on gastroduodenal ulcer models in rats and guineapigs

The methanolic fraction of P. indica root extract was found to possess significant antiulcer activity in different experimental animal models. In preventive antiulcer tests, significant protective actions in acetylsalicylic acid, serotonin and indomethacin-induced gastric lesions were observed in experimental rats. The extract also afforded significant protection to chemically-induced duodenal lesion in guineapigs. Significant enhancement of healing process in acetic acid-induced chronic gastric lesions were also observed in the extract-treated animals.     

Continuous recording of urethral activity in healthy female volunteers

The pressure variations at the maximal urethral closure pressure (MUCP) were continuously recorded in healthy female volunteers by means of a two-point microtip transducer catheter for one hour. Before the investigation a normal voiding was assured objectively and bladder instability was excluded. All women showed pressure variations both at the MUCP and more distally. The pressure variations, from 3 to 66 cm H₂O, showed rhythmicity and three frequency ranges could be identified. Slow pressure waves with a frequency of one in eight to 19 minutes were observed. Relatively fast-pressure waves were observed (one every one to four minutes) and relatively fast-frequency pressure waves were observed (rate: one to eight per minute). The pressure variations of the urethra seem to be an aspect of normal urethral physiology possibly contributing to continence and urinary tract infection prevention.     

Changes in the Eeg Background Activity of Children with Acute Lymphoblastic Leukemia During Cytotoxic Therapy

Thirteen children with acute lymphoblastic leukemia (ALL) were investigated before and during cytotoxic therapy. EEG findings were correlated with the clinical course and the therapy protocol and compared with normal data obtained from 295 healthy children. Frequency analysis of the background activity of the EEG revealed an initial slowing of the background activity prior to therapy and further slowing each time a combination of vincristine (VCR), daunorubicine (DAU) or adriblastine (ADR), prednisone (FRED), and L-asparaginase (L-ASP) was administered. The slowing of the background activity correlated only with the administration of these drugs. DAU, ADR, and FRED are not known to influence the EEG; therefore, VCR and L-ASP remain the primary candidates responsible for the central nervous system alteration.     

EDTA Registry centre survey, 1986. Report from the European Dialysis and Transplant Association Registry

This paper summarises the information given on the 1986 EDTA Registry centre questionnaire which was returned by 82% of the 2,065 known dialysis and transplant centres in 33 European countries. Information is given on the number of patients alive on haemodialysis according to the type of dialysis facilities available where the patient was receiving dialysis and the number of patients receiving special types of dialysis. The centre questionnaire also included questions on testing for HIV infection, serological evidence or symptoms of AIDS and the diagnosis of hepatitis B in patients and staff. The data given in response to these questions are presented together with data on the involvement of dietitians and social workers in the treatment of patients with end stage renal failure. Finally, information on transplant activity in Europe and the treatment policies of transplanting centres is provided.     

Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates

Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC₅₀ = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC₅₀ = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery.     

The effect of bacterial melanin on electrical activity of neurons of the substantia nigra under conditions of GABA generation

The changes in spike activity of single neurons of the compact part of the substantia nigra, evoked by nucleus caudatus stimulation under conditions of long-term registration of the single and multiple, isolated and combined actions of GABA, GABA-amide, glutamine, and ethanolamine-O-sulfate (EOS) were studied in albino rats. Inhibition of poststimulus activity under GABA action was recorded and the inhibitory effect of GABA-amide was revealed. Primary excitatory and subsequent inhibitory effects of glutamine in combination with EOS were shown. The subsequent administration of bacterial melanin, synthesized by a mutant culture of Bacillus thuringiensis (BT-M) evoked a clear-cut and prolonged excitatory reaction during all the combined actions of GABA, GABA-amide, glutamine, and EOS. Preliminary administration of BT-M abolished the inhibitory poststimulus effects of GABA, GABA-amide, and EOS, as well as glutamine-induced excitation.