Long-sleep (LS) and short-sleep (SS) mice were pretreated with either propranolol or phentolamine, followed by a hypnotic dose of ethanol. Pretreatment with propranolol, but not phentolamine, significantly reduced ethanol sleep time in LS mice. The SS mice were not affected. In a second study propranolol pretreatment was given subsequent to ethanol at various doses, different for each line, that produced similar sleep time durations in both lines. Under these conditions, propranolol decreased sleep time in both LS and SS mice. These data lend support to the idea that noradrenergic mechanisms play a role in the mediation of the hypnotic effects of ethanol.

Ethanol-sensitive long-sleep mice showed greater sensitivity to ethanol-induced hypothermia whereas the less sensitive short-sleep mice showed greater sensitivity to morphine-induced hypothermia. The short-sleep mice, but not the long-sleep mice, displayed a degree of cross-tolerance to the hypothermic effects of ethanol following repeated exposure to morphine.

The choice of experimental subjects for research in neurobehavioral toxicology influences the questions that may be asked and the generality of findings obtained. In particular, the relative merits of "random bred" animals, heterogeneous stocks, selected lines, and inbred strains are discussed. Several aspects of genetic-environmental coaction that may influence data are described, and general issues for their analyses discussed.

The behavioral effects of histamine agonists and antagonists were investigated in mice subjected to handling, injections, and transport to a novel observation chamber. Relative to control mice subjected to this treatment, mice treated with various doses of an H1 histamine receptor agonist or an H2 receptor antagonist displayed significantly elevated levels of grooming. On the other hand, treatments with either an H1 histamine antagonist or H2 receptor agonist attenuated stress-induced grooming. These effects of histaminergic agents were probably not due to their general effects on behavioral arousal, but rather may be specific to neurohumoral mechanisms mediating grooming. We have postulated that H1 histamine receptor activation is involved in the excessive grooming induced by the stressor of being handled and placed in a novel environment, whereas H2 receptor activation attenuates this phenomenon via inhibitory control of H1 histamine neural elements.

The results of previous studies have suggested that periadolescent rats are differentially affected by catecholaminergic agents, when compared with younger or adult animals. Since dopamine-opiate interactions have been demonstrated in rats, the present study was conducted to evaluate the behavioral responsivity of periadolescent and adult rats following doses of morphine ranging from 1 to 10 mg/kg i.p. The responses measured included matrix crossings, rearing, grooming, auto-directed stereotyped behavior and gnawing, and were recorded continuously from 30 to 90 min post-injection. When indicated, scores on each measure were transformed to control for differences observed in the baseline (saline) groups. Analyses of all measures revealed a significant effect of morphine dose, although the shape of the dose-response curve differed for individual responses. In addition, those measures which might be considered locomotor responses (matrix crossing, rearing), as well as grooming, revealed significant main or interactive effects of age. In contrast, those measures characterized as stereotyped behaviors (auto-directed stereotyped behavior and gnawing) revealed no differential effect in periadolescent animals relative to adults. Since locomotor responses and stereotyped behavior have been suggested by previous research to be mediated by the mesolimbic and extrapyramidal dopamine systems, respectively, these results further support the previously suggested hypothesis of the delayed ontogeny of mesolimbic relative to extrapyramidal dopamine pathways.

Mice which have been selectively bred for differences in sensitivity to acute doses of alcohol have also been shown to differ in severity of seizures upon withdrawal from chronic alcohol administration. We investigated the responsiveness of these mice to withdrawal from chronic morphine treatment. Mice were made dependent on morphine via pellet implantation, and withdrawal was precipitated with naloxone challenge. Mice which are less sensitive to the hypnotic effects of ethanol (short sleep: SS) displayed more jumping and wet dog shakes during withdrawal than did the more sensitive long sleep (LS) mice. In addition, the amount of jumping was dependent on the dose of naloxone in both lines. Differences between lines in naloxone precipitated withdrawal may reflect differences in alterations in extrapyramidal dopaminergic activity, but other substrates for the observed differences cannot be discounted. Finally, the observed difference between SS and LS mice in severity of morphine withdrawal parallels the previously reported difference between these lines in seizure severity during withdrawal from alcohol.