Joyce M. Rawleigh

The effects of restraint stress on voluntary ethanol consumption in rats.

Sixty Wistar rats (Rattus norvegicus) were assigned to 4 groups of 15 rats each: ethanol stress (ES), ethanol no-stress (EN), isocaloric stress (IS) and isocaloric no-stress (IN). The effect of restraint stress on daily intake of ethanol and a 0.72% solution of glucose was examined in an ABA design (stress-no stress-stress). During the stress phases, 2 groups were subjected to daily 15-min restraint stress, whereas 2 groups were placed in different cages for 15 min as a control. All 4 groups were then given 6-hr access to their assigned liquid alone for 4 days followed by a choice between their assigned liquid and water on the 5th day. The ES group significantly increased their ethanol intake (g/kg) compared to the EN group on choice days but not on forced days. Percentage preference for ethanol was significantly greater and increased at a faster rate over the 75-day testing period compared with the EN group. However, total ethanol consumption (g/kg) and percentage preference did not vary as a function of phase. It is notable that the effects of restraint stress on ethanol self-administration persisted even after the stress schedule was removed.

Concurrent self-administration of ethanol and an alternative nondrug reinforcer in monkeys: effects of income (session length) on demand for drug

Eight rhesus monkeys (Macaca mulata) were trained to self-administer orally delivered ethanol (8%) and saccharin (0.03 or 0.3% wt/vol) or water under concurrent fixed-ratio (FR) schedules. The FR requirement for saccharin was fixed at 32, while the FR for ethanol was varied (4, 8, 16, 32, 64 and 128) in a nonsystematic order to assess demand for drug. Demand was defined as consumption plotted as a function of price (FR). Income was defined as the duration of access to available resources. Income was varied by allowing access to the concurrently available liquids 20, 60 or 180 min per day. Order of testing was counter-balanced across monkeys. Saccharin deliveries were much higher than ethanol deliveries under the 180-min income condition; however, they were lower than ethanol deliveries when income was reduced to 20 min and the ethanol FR was 4, 8 or 16. Thus, when the price of drug was relatively low, consumption of drug exceeded that of the nondrug reinforcer, and that relationship was reversed as income decreased. Saccharin deliveries sustained a proportionally greater reduction due to decreased income compared to ethanol deliveries. As income decreased from 180 to 20 min, saccharin deliveries were reduced by an average of 79.1% (across ethanol FR conditions) while ethanol deliveries were reduced by an average of 41.2 and 40.8% when concurrent saccharin or water were available, respectively; thus, drug self-administration was more resistant to income changes than saccharin. The demand for ethanol was shifted downward in a parallel fashion as income decreased. As ethanol cost (FR) increased, there were proportionately greater decreases in ethanol intake when saccharin was concurrently available compared to when water was available. There was a 35–50% reduction in ethanol deliveries due to concurrent saccharin (versus water) at FR 4, compared to a 55–75% reduction at FR 128. Cost of ethanol (FR), income level and the availability of a nondrug reinforcer are all variables that modify ethanol-reinforced behavior, and income alters the relative preference for a drug versus nondrug reinforcer.

Differential effects of prior dominance or subordination experience on conspecific odor preferences in mice

Preferences for the soiled bedding odors of familiar and unfamiliar conspecifics were assessed among male mice rendered dominant or subordinate by a series of resident-intruder encounters. Alpha males preferred the odors of their familiar antagonist most strongly. Subordinates, in contrast, showed strongest preferences for unfamiliar females and a weaker preference for alpha odors. When female odors were eliminated from the preference test, alphas continued to show the strongest preference for familiar subordinate odors while subordinates displayed roughly equivalent preference for the odors of familiar alphas and unfamiliar males. It is suggested that the apparent mild preferences of subordinates for dominant conspecific odors reflects fear motivated risk assessment. In contrast, approaches of dominants to subordinate odors seems to be appetitively motivated. Generally recognizable subordination odors may be useful to unfamiliar males in recognizing exploitable resources.

Effects of eltoprazine hydrochloride on exploratory behavior and social attraction in mice

The effects of eltoprazine (DU 28853) on exploratory behavior and conspecific social attraction were examined in four experiments. Drug treatments somewhat enhanced three forms of exploratory behavior but decreased social attraction. The results indicate that eltoprazine, in sharp contrast to fluprazine, weakly ameliorates neophobic responses. Both eltoprazine and fluprazine seem to increase the aversiveness of encounters with other organisms, however. The latter effects may be mediated, in part at least, by some alteration in olfactory function.

Effects of eltoprazine hydrochloride on reactivity to conspecific or novel odors and activity

Treatment with eltoprazine (DU 28853) increased the number of entries by male mice into compartments containing the odors of male and female conspecifics. This effect was most pronounced when odors were provided by previously defeated males. In contrast, the drug had no effect upon responsiveness to the odors of cinnamon and chocolate. The results suggest that eltoprazine may selectively increase reactivity to conspecific odors and that this effect is further enhanced by agonistic experience. Eltoprazine also substantially increased activity levels in all experiments. Since hyperactivity occurred both in the presence and absence of conspecific odors, however, the drugs effects on activity and olfaction seem to be largely independent. The results suggest that the aggression-modulating effects of eltoprazine, as well as other drugs, may be mediated in part by their effects on normal olfactory function.

Effects of yohimbine on novel open field exploration of mice

The effects of the anxiogenic compound yohimbine on exploration of a novel open field was investigated. The drug had no effect on latency to enter the open field but produced a marginally significant increase in number of open field entries. The results suggest that yohimbine may have behavioral stimulant and/or anticonflict properties under some testing conditions. Such effects may limit its usefulness as a research tool for the study of anxiety.

Yohimbine does not impair performance on an olfactory discrimination

The anxiogenic compound yohimbine inhibits intermale attack and increases conspecific sniffing; however, it decreases preference for male odors. This experiment explored the generality of yohimbine’s olfactory effects by assessing drug effects on searching for buried food items. Drug treatment had no effect on the location of buried or unburied rewards. This finding suggests that yohimbine’s olfactory effects may be restricted to conspecific odors. These findings underscore the need for further study of olfactory function among drugs having antiaggressive effects in common.

Resident-Intruder Paradigms and Antiaggressive Drugs: Some Further Data

Treatment with a number of phenylpiperazine drugs induces a selective inhibition of attack behavior during resident-intruder encounters which has been interpreted as reflecting a drug-induced “serenic” state. Treatment with two well-characterized anxiogenic compounds (yohimbine, FG 7142), however, also closely mimicked the effects of phenylpiperazines on such attack. In addition, studies with two of the serenics revealed that they increased avoidance induced by novel stimuli (fluprazine) and/or nonaggressive conspecifics (fluprazine and eltoprazine). These data not only suggest that phenylpiperazines may be more properly characterized as anxiogenic, but the data also bring into question the usefulness of behavioral profiles derived exclusively from resident-intruder tests to infer anxiolytic or anxiogenic drug actions. Novelty-induced tearfulness is suggested to provide a useful instrument for the detection of generalized anxiolytic or anxiogenic effects whereas nonagonistic social interactions reveal more specific drug effects on reactivity to conspecifics. In addition, the fact that the attack-suppressing effects of fluprazine and yohimbine are also accompanied by increased sniffing behavior and altered conspecific odor preferences strongly suggests the need for a careful examination of olfactory function in the assessment of any putative antiaggressive drug.