Robert A. Levitt

Morphine and shuttle-box self-stimulation in the rat: a model for euphoria.

In a shuttle-box self-stimulation paradigm, analgesic doses of morphine increase the amount of time a rat leaves rewarding brain stimulation on, without altering average OFF times. This paradigm may serve as a model for the euphoria induced by narcotic drugs and as a useful tool for evaluating the reinforcing effects of drugs.

Drinking elicited by injection of eserine or carbachol into rat brain

Abstract Two experiments investigated the induction of drinking that results from eserine injections into rat limbic system nuclei. In the first, a high correlation was found between the neural sites from which drinking was elicited by eserine and those from which drinking was elicited by carbachol. In the second, it was found that central atropine injection into one cholinergically positive drinking site inhibited the drinking elicited by eserine at a second such site. These results suggest a physiological role of the cholinergic drinking substrate and further confirm the diffuse distribution of this substrate.

Neural activity changes correlated with central anticholinergic blockade of cholinergically-induced drinking.

In the rat, microinjections of carbachol into the septal area elicited water ingestion and increased multiple unit activity at this site and also the noninjected lateral hypothalamus. Carbachol injection into the lateral hypothalamus also elicited water ingestion, but multiple unit activity did not increase in this structure, although it did in the noninjected septal area. If carbachol was injected into one of these sites and isotonic saline into the other (conditions comparable to those for which drinking has been previously demonstrated), increased multiple unit activity was still found. However, if carbachol was injected into one of these sites and atropine into the other (conditions comparable to those for which the blockade of drinking has been previously demonstrated), the increases in multiple unit activity were blocked. Carbachol-elicited drinking may result from neural activity changes similar to those recorded in this study, and atropine may inhibit carbachol-elicited drinking by inhibiting such neural firing changes.

Etorphine and shuttle-box self-stimulation in the rat

Rats were trained to turn rewarding electrical brain stimulation on and off by crossing back and forth in a shuttle-box. Moderate doses of the narcotic analgesic, etorphine, increased mean ON times while having little effect on OFF times. Tolerance did not develop to the reward enhancement action over five consecutive days of injections. This paradigm seems valuable for exploration of the reinforcing properties of narcotic drugs.

Drinking elicited by intracranial microinjection of angiotensin in the cat

Abstract When the level of angiotensin II in the brain is augmented by microinjection of this substance the fully-hydrated cat drinks copiosly. The magnitude of this response is closely dependent upon the dose of angiotensin II injected. The latency of the drinking response was 1–2 min for each of the doses of angiotensin employed in this study. This is the first report of the induction of thirst in cats by central chemical stimulation and furthers the concept that angiotensin II is a potent dipsogen in vertebrates.

Cortical spreading depression and thirst

Abstract Bilateral, but not unilateral, cortical spreading depression inhibited drinking of water, whether motivated by water deprivation or cholinergic brain stimulation. This inhibition of behavior does not appear to be specific to cholinergic mechanisms, thirst, or appetitive responding. Rather, a more general blocking of neurobehavioral systems due to cortical deactivation seems likely.

Etorphine induction of analgesia and catatonia in the rat: Systemic or intracranial injection

Abstract Etorphine was injected into the rat either intraperitoneally (i.p.), in the periaqueductal gray (PAG) region of the midbrain, or in the cerebellum (CB). The flinch-jump technique was used to measure analgesia and the bar test to assess catatonia. Etorphine doses were 5, 10, 50 or 100 μg/kg (i.p.). The doses of etorphine administered to the PAG were 0.1, 1.0, 2.0 or 3.0 μg. The dose of etorphine administered to the cerebellum was 2.0 μg. The effective doses into the PAG for producing both analgesia and catatonia were about 15 times less than the intraperitoneal doses, suggesting central mediation of these actions, involving the PAG and perhaps other central neural sites. Injection of 2.0 μg etorphine into the cerebellum did not cause analgesia or catatonia. There was a high correlation between the production of analgesia and of catatonia suggesting a common factor in these actions, at least as measured in this experiment.

Effects of cholinergic brain injections on mouse killing or carrying by rats

Some rats will consistently kill a mouse placed in their cage, others will simply carry the mouse around the cage (without killing), while about 50% of the rats show neither behavior. This experiment investigated the effect of chemical brain stimulation with a cholinergic or anticholinergic drug on mouse killing and mouse carrying by rats. Carbachol significanly inhibited both killing and carrying, while atropine had no effect on the behaviors. These data are inconsistent with previous studies implicating cholinergic mechanisms in the facilitation of mouse killing. The implications of this study are discussed.

Dose-response analysis of angiotensin- and renin-induced drinking in the cat.

Abstract A dose-response study of drinking elicited by angiotensin-II in the cat found a threshold below 125 ng and a maximally effective dose of 500 to 1000 ng. For renin, the threshold was between 1 and 5 Goldblatt milliunits and the maximally effective dose above 45 Goldblatt milliunits. The dose-response curves for water consumption elicited by these two drugs and the dose-response curves for latency to drink did not differ in the 5 different neural sites examined (septal region, caudate nucleus, preoptic area, lateral hypothalamus and lateral ventricle). Although cats stimulated with angiotensin-II drank at a similar rate to water deprived animals, renin-stimulated cats drank significantly more slowly.

Mouse killing and carrying by Maudsley and Long-Evans strain rats

The incidence of mouse killing and mouse carrying in three strains of rats was investigated. Both sexes of the Maudsley reactive, Maudsley nonreactive, and Long-Evans rats served as subjects. The highest incidence of mouse killing was observed among male reactives (44%), an intermediate incidence in Long-Evans males (24%), and a low incidence in the Maudsley nonreactive males (8%). Female reactives, female Long-Evans, and female nonreactives showed similar low incidences of killing (14%, 13%, and 11%, respectively). Male and female nonreactives and female reactives showed the highest percentages of mouse carrying (78%, 87%, and 81%, respectively) with male reactives at an intermediate percentage (48%) and Long-Evans males and females at the lowest percentage (28% and 26%). The possible relationship between selective breeding for open-field reactivity and the incidence of mouse killing is discussed.