Oxytocin modulates behavioural adaptation to repeated treatment with cocaine in rats.

Behavioural adaptation to and the effects of the neurohypophyseal peptide, oxytocin, on repeated treatment with cocaine were investigated in rats. The content of immunoreactive oxytocin in the plasma, hypothalamus and different limbic structures in the brain were also studied after treatment with cocaine, identical to that used in the behavioural experiment. Repeated administration of cocaine (7.5 mg/kg, s.c.) produced a behavioural tolerance to the stereotyped sniffing-inducing effect of the challenge doses (1.875, 3.75 and 7.5 mg/kg, s.c.) of cocaine on the fifth day, which was demonstrated by parallel shifting of the dose-response and time-effect curves of the test doses of cocaine. The development of tolerance was inhibited by pretreatment with oxytocin (0.05 micrograms, (s.c.), administered before each daily injection of cocaine. A smaller dose of oxytocin (0.005 micrograms, s.c.) had no effect in this model. A decreased amount of immunoreactive oxytocin was detected in the plasma, in the hypothalamus and in the hippocampus, after repeated treatment with cocaine. Replacement of oxytocin by local injection (100 pg) into the ventral hippocampus, before each daily administration of cocaine, prevented the development of tolerance to cocaine. These results suggest that endogenous oxytocin, localized in limbic-forebrain areas, may have an important regulatory role in the development of behavioural changes induced by the repeated administration of cocaine.

Effects of brain natriuretic peptide on effects of morphine in mice.

Brain natriuretic peptide (BNP) is a member of the natriuretic peptide family. The effects of intracerebroventricularly administered BNP (in 0.002-200 ng doses) on the analgesic, tolerance-inducing and dependence-inducing actions of morphine were investigated in adult male CFLP mice. Graded doses of BNP centrally did not affect pain sensitivity itself in a tail-flick test. However, different doses of BNP depressed the acute nociceptive effect of a single subcutaneous dose of morphine (5 mg/kg), and BNP attenuated the development of acute and chronic tolerance to morphine. Withdrawal signs were studied by injecting naloxone (1 mg/kg s.c.). There was no significant difference in symptoms between the tolerant group and animals treated with BNP. The data obtained indicate that BNP can modify the analgesic action of morphine.

C-type natriuretic peptide can modify the acute and chronic effects of morphine.

Different doses (0.2-200 ng) of C-type natriuretic peptide (CNP) were administered into the lateral brain ventricle, and morphine (5 mg/kg) was injected subcutaneously. The analgesic effect was measured in a tail-flick test, in CFLP mice. CNP administered centrally did not itself affect pain sensitivity, but it depressed the acute antinociceptive effect of morphine 30 min after icv (0.2, 2 or 20 ng) CNP administration and the 2 and 20 ng doses also decreased this action after 60 min. CNP in a 0.2 or 200 ng dose blocked the development of acute tolerance to morphine after 30 min, as did the 200 ng dose at 60 min. CNP in a 0.2 ng dose blocked the development of chronic tolerance to morphine after 30 min, but there was no effect at 60 min. Morphine withdrawal signs were studied by injecting naloxone (1 mg/kg sc). There was no significant difference in symptoms between the tolerant group and the animals treated with CNP.

Selective attenuation of cocaine-induced stereotyped behaviour by oxytocin: putative role of basal forebrain target sites.

The effects of oxytocin (OXT), arginine- and lysine-vasopressin (AVP and LVP) and an OXT-receptor antagonist on cocaine-induced sniffing behaviour were investigated in rats. OXT, but not AVP or LVP injected subcutaneously (s.c.) attenuated cocaine-induced sniffing. The effect of OXT (s.c.) was inhibited by an OXT-receptor antagonist administered intracerebroventricularly (i.c.v.). I.c.v. administration of different doses of OXT in nanogram quantities caused a dose-dependent attenuation of cocaine-induced sniffing. Local cerebral microinjection of OXT into the accumbens nucleus and olfactory tubercle but not into the olfactory nucleus, central amygdaloid nucleus or caudate nucleus, inhibited the cocaine-induced sniffing behaviour. These results demonstrate that OXT selectively attenuates the cocaine-induced stereotyped behaviour through basal forebrain target sites.

Effects of secretin on acute and chronic effects of morphine.

The effects of intracerebroventricularly (ICV) administered secretin on the analgesic, tolerance-inducing, and dependence-inducing actions of morphine were investigated, in adult, male CFLP mice. Secretin administered doses ICV did not itself affect pain sensitivity in a heat-radiant tail flick test. However, it depressed the acute nociceptive effect of a single subcutaneous (SC) dose of morphine (4 mg/kg) after ICV (1 or 10 ng/animal) secretin administration. A dose of 10 ng secretin facilitated the development of acute morphine tolerance. On the other hand, none of the doses applied had any influence on chronic morphine tolerance, where animals were implanted SC with a morphine- containing pellet and the pain sensitivity was measured 3 days later. Morphine withdrawal signs were also evaluated by injecting naloxone. In a 100-ng dose, secretin increased the latency of the withdrawal jumping response; the peptide did not modify the other abstinence signs. These data suggest that central secretin administration can modify the analgesic effect of morphine.

[Comparative study of the role of CA 19-9, CA 72-4 and CEA tumor antigens in the diagnosis of pancreatic cancer and other gastrointestinal malignant diseases]. / A CA 19-9, CA 72-4 és a CEA tumorantigének összehasonlító vizsgálata a pancreascarcinoma és az egyéb emésztöszervi malignus betegségek diagnózisában.

The diagnostic value of CA 19-9, CA 72-4 and CEA was evaluated in 291 patients (including 39 with pancreatic cancer, 32 with gastric cancer, 36 with colorectal cancer and 40 with chronic pancreatitis). These markers were determined in the serum by chemiluminescence immunoassay (CA 72-4) or microparticle enzyme immunoassay (CA 19-9 and CEA) methods. In serodiagnostic evaluations relating to pancreatic cancer, CA 19-9 proved superior to CA 72-4 and CEA (sensitivity: 79.5 vs. 56.5 and 62.5%; specificity: 84.1 vs. 77.9 and 77.2%; diagnostic accuracy: 85.9 vs. 75.8 and 75.7%, respectively). For gastric carcinoma, CA 72-4 appeared the most sensitive: 53.1% of all patients were identified with a specificity of 78.9% and a diagnostic accuracy of 75.4%. In the diagnosis; of colorectal cancer, CEA exhibited the highest sensitivity (63.9%) and diagnostic accuracy (76.2%). Elevated CA 19-9 levels were obtained in only 7.7% of patients with chronic pancreatitis. Tumor marker determination is useful in the diagnosis of gastrointestinal malignancies: the marker of choice in pancreatic cancer is CA 19-9, in gastric cancer it is CA 72-4 and in colorectal cancer it is CEA. CA 19-9 is effective in discriminating between pancreatic cancer and chronic pancreatitis.