PubMed Health⌕ Search

Biomedical subjects

N R Shapiro

Publications and source records attributed to N R Shapiro.

8 recordsLinked to original sources

The role of associative factors in tolerance to the hypothermic effects of morphine in mice.

Associative learning theories of drug tolerance emphasize the importance of stimuli which predict drug administration. One such model holds that drug tolerance is due to the development of a conditional response (CR) which is directionally opposed to the unconditional response (UCR) to the drug. By virtue of their opposing natures, the overlapping occurrence of CR and UCR is seen as a diminished response, i.e., tolerance. The present experiments tested the predictions of this model using two doses of morphine, and included truly random controls to examine the role of excitatory and inhibitory conditioning in tolerance. Tolerance was greatest in mice administered morphine in the context of stimuli previously paired with drug administration, intermediate in random controls, and least or absent in mice administered the drug in the presence of cues paired with vehicle injections. No direct evidence of a compensatory CR which could offset morphine's hypothermic effect was obtained in placebo test sessions, nor was evidence for such a response obtained in cross-drug tests with amphetamine and apomorphine.

Animals↗

Cross-motivational effects of inescapable shock are associative in nature.

Exposure to inescapable shock interferes with the subsequent acquisition of an appetitive operant. This deficit may be due to either associative interference or activity reduction from the inescapable shock pretreatment. The relative importance of these two factors was examined by using an appetitive response choice discrimination procedure and concurrently measuring activity. Experiment 1 demonstrated separate associative and activity effects of inescapable shock, in that the animals exposed to inescapable shock made more incorrect responses than controls and were lower in activity. Experiment 2 demonstrated that these effects resulted from the uncontrollability of the shock, not from shock exposure per se. In Experiment 3, residual effects of inescapable shock were investigated by exposing animals to discrimination reversals. On these tests, inescapably shocked animals showed performance inferior to nonshocked controls, a result indicating that the effects of inescapable shock are not completely reversed by experience with contingent reward in the discrimination task. No evidence of an activity deficit was observed during this discrimination reversal. These results strongly suggest that associative factors play a more important role than activity reduction in mediating the effects of inescapable shock, at least when these are measured in an appetitive context.

Animals↗

Avoidance behavior in rats selectively bred for differential alcohol sensitivity.

"Most affected" (MA) and "least affected" (LA) rats, bred for extremes in motor impairment following an alcohol challenge, differed in their performance on two active avoidance tasks. In two-way shuttle avoidance, the MA line performed significantly better than the LA group, both in terms of response latencies and percent avoidances. The inferior performance of the LA line persisted across the 15 days of testing, and appeared to reflect an difference in asymptotic performance levels. In one-way avoidance, the MA line showed significantly better acquisition than the LA group; however, this difference dissipated across the 3 days of training. When tested following alcohol administration in either the one- or two-way avoidance paradigm, the MA rats showed a greater performance deficit than LA animals. These data were interpreted as indicating the generality of alcohol-related line differences to a situation motivated by aversive consequences. Moreover, the line difference in avoidance acquisition represents one of the few non-drug-related phenotypic differences that have been found in these lines. In previous generations, disparate base rates of wheel running have been reported, and the data presented here confirm and extend this finding.

Animals↗

Lack of response inhibition in rats prenatally exposed to alcohol.

Offspring of mothers who consumed either 32, 19, 8, or 0% of their daily caloric intake in the form of ethanol during pregnancy were tested for passive avoidance. At 18 days of age, the number of trials to criterion and the within-group variability were direct functions of the amount of ethanol consumed by the mother during pregnancy. At 41--53 days of age, alcohol-treated pups still required more trials to criterion than controls and had faster speeds into the shock compartment on the first trial. When the progeny of mothers consuming either 35, 17, or 0% ethanol-derived calories during pregnancy were compared for conditioned taste aversion to a lithium chloride solution, a linear dose-response function was again evident. Animals in the alcohol-treated groups showed less suppression of drinking than controls. These investigations indicated that the effects of alcohol exposure in utero were manifested in behavioral outcomes involving response inhibition that were not correlated with the more familiar physical symptoms.

Animals↗

Hypnotic susceptibility to various depressants in rats selected for differential ethanol sensitivity.

MA rats, bred for greater motor impairment following subhypnotic doses of ethanol, were found to be more sensitive to the hypnotic effects of phenobarbital and chloral hydrate than were LA rats. In addition, the previously reported finding of a difference between the two lines of rats in duration of loss of righting reflex following a hypnotic dose of ethanol was replicated. The results are discussed in terms of a phenotypic difference in central nervous systems sensitivity to a range of sedative-hypnotics.

Animals↗

Nose-poking and head-dipping behaviors in rats prenatally exposed to alcohol.

In three experiments pregnant female rats consumed liquid diets containing various amounts of the total calories in the form of ethanol. In the first study, offspring of these females were tested in a nose-poking paradigm. The frequency of this response was found to be a direct function of the level of alcohol exposure in utero. In a second study when nose poking produced the onset of a dim light, animals prenatally exposed to alcohol were again found to poke more often, and this effect was not attenuated by preweanling handling. Finally, the generality of these findings became evident when head dipping rather than nose poking was examined; head-dip frequency was higher in alcohol-exposed offspring, and this effect was independent of stimulus complexity. Additionally, offspring body weights and survival rates following this prenatal alcohol exposure are presented.

Aging↗

Response perseveration in rats exposed to alcohol prenatally.

Pregnant female rats consumed liquid diets containing either 35, 17, or 0% of the total calories as ethanol. Offspring of these females were tested for spontaneous alternation at 21 days of age and for reversal learning in a T-maze shock-escape paradigm at 20--21 days of age. In the spontaneous alternation test, rats exposed to alcohol prenatally took more trials than controls to enter the goal compartment opposite to that initially entered. In the T-maze escape study, alcohol-exposed offspring made more mistakes prior to criteron and more mistakes per trial than controls when the previously incorrect goal was made safe during reversal learning. In both studies linear dose-response functions were found. Furthermore, there was a significant tendency for the within-group variabitliy to increase as the level of prenatal exposure increased, perhaps indicating that the incidence as well as the severity of behavioral dysfunction was dose dependent. The results are interpreted in terms of a delay in the development of a central inhibitory system.

Animals↗