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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.

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.

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.

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.