Search NEL Online

Journal Article 2010; 31(5): 708-716 PubMed PMID: 21173740 Citation  Keywords:  Androstatrienes:administration & dosage, Animals, Brain:drug effects, Enzyme Inhibitors:administration & dosage, Female, Gestational Age, Injections, Intraperitoneal, Male, Pharmaceutical Vehicles:administration & dosage, Pregnancy, Prenatal Exposure Dela.   

OBJECTIVE: In order to clarify the effect of the prenatal (PN) treatment of the drug 1,4,6-androstatriene-3,17-dione (ATD) which blocks the conversion of testosterone into estradiol on male sexual behavior of the rats offsprings, from the effect of the mild stress induced by the PN administration of the Propylene glycol (PG), the vehicle used to dissolve ATD.

METHODS: Pregnant Wistar rats were divided into three groups. The CON group did not receive any kind of treatment. The other two groups (PG and ATD) were injected i.p. during gestation (days 11-22) with 0 and 5 mg of ATD, dissolved in 0.1 ml of PG, respectively, doses reported by other authors. Sexual performance of the male pups was analyzed three months later in four successive tests.

RESULTS: In the first sexual test of these naive rats, the percentage of males mounting, intromitting, ejaculating and the ejaculation frequency of the ATD group decreased significantly in comparison with the CON group. Also in the first and 4th tests, mounting, intromission and ejaculation latencies, as in the post-ejaculatory refractory period, ATD group, was significantly longer in comparison with the CON group. PG males showed a male sexual behavior (MSB) similar to that observed in the ATD group, but the differences did not reach statistical significance when they were compared with the CON group.

CONCLUSION: We considered that the PN stress induced by the daily administration of PG and ATD, results in a slower execution of the MSB in both groups and avoid distinguish the effect of the ATD. Then chronic PN injections, as a route of administration, could act as mild stressor and may have additive effects on drugs affecting brain sexual differentiation....

Read abstract  Full text PDF

Journal Article 2009; 30(1): 144-152 PubMed PMID: 19300402 Citation  Keywords:  Animals, Bradykinin:administration & dosage, Bradykinin Receptor Antagonists, Diabetes Mellitus, Experimental:chemically induced, Diabetic Neuropathies:chemically induced, Drug Evaluation, Preclinical, Enzyme Inhibitors:administration & dosage, Hyperalges.   

PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated.

METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto.

RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy.

CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care....

Read abstract  Full text PDF