Transition frequencies as additional measurements for assessing anxiolytic drug activity in the elevated plus-maze test

128

In the present study, it is investigated whether the occurrence of SWD and of other oscillations is facilitated by TSD. Eight male adult WAG/Rij rats were chronically provided with cortical EEC and nuchal EMC electrodes. Animals were recorded for 24 h to obtain a base-line; next they were deprived of total sleep for 12 h during the light phase. TSD was accomplished with an arousal technique: at detection of sleep-onset the cage of the animal was shaken until the rat awakened. TSD appeared to be effective: a reduction of 78% was accomplished, eliminating all REM sleep and almost all deep sleep. The number of SWD was enhanced during the first four hours of the TSD period, followed by a decrease after eight deprivation hours. These results may be explained by the presence of an initial increase in sleep pressure and in transitions into light slow wave sleep, gradually changing into the presence of periods during which awakenings were immediately followed by quick transitions into deep sleep; the latter state being unfavourable for the appearance of SWD. Furthermore, another result was that in the course of the TSD, arousing of the animal was followed by oscillations in the EEC about 2 s after the shaking of the cage had ended.The probability of an oscillation to occur following an arousal increased about 4.3 times as TSD proceeded. These results indicate that TSD facilitates the occurrence of two types of oscillations: first, the characteristic SWD in the beginning of the TSD period, and later on the short lasting rhythmic phenomena. Whether both types of oscillations should be considered as representatives of one class is an important question for future research, as well as the question whether the arousal-induced rhythmic oscillations are a common phenomenon or unique to epileptic rats.

Transition frequencies as additional activity in the elevated plus-maze test

measurements

for

assessing

anxiolytic

drug

U. Falter, J. Gobert and A.J. Cower UCB-Pharma,

CNS Department,

Chemin

du Foriest, B-1420

Braine-I’Alleud,

Belgium

The elevated plus-maze is a standard rodent test of anxiety aimed at detecting potential new anxiolytic drugs. It consists of a cross-maze, mounted 70 cm above floor level, with two open and two closed arms, like arms facing one another. As rodents spontaneously tend to avoid the open arms, anxiolytic activity is classically inferred from the ease with which drug-treated animals increase the number of visits onto and/or the time spent on the open arms. Recent studies (Moser, 1989) have shown that these measurements are not sufficient to reliably detect new anxiolytic compounds. The aim of the present experiments was to investigate whether information provided by the spatial exploration strategy could contribute to a better appreciation of the anxiolytic activity of drugs in this test. Besides the standard measurements, we therefore also calculated arm-transition frequencies, expressed as percentage of closed-closed, or open-open transitions, and percentage of open-closed, or closed-open transitions. Chlordiazepoxide (CDP), O-20 mg/kg po 60 min, or O-IO mg/kg ip 30 min, was used as the reference drug and its effects were evaluated either on a

129

standard plus-maze,

or on an inverted plus-maze with unlike arms facing one another.

CDP, as expected, significantly increased the percentage of open-arm-visits and the time spent on the open arms. This effect was, in the standard plus-maze, mainly due to an increase of the open-open transitions, a phenomenon which was not apparent in the inverted plus-maze and could be attributable to stereotypy. Arm-transition frequencies thus appear to help separate true anxiolytic activity from stereotypy, an undesirable side-effect of CDP, and therefore could constitute an important additional parameter in the evaluation of other anxiolytic drugs. References Moser,

P.C., 1989. An evaluation

Psychopharmacology,

of the elevated

plus-maze

test using the novel anxiolytic

buspirone.

99: 48-53.

Steroid specificity in the control immunocytochemical study

of aromatase

by androgens

and

estrogens:

An

A. Foidart, R. Loeffen and J. Balthazart Laboratory

of General

and Comparative

Biochemistry,

University

of Li&ge, Belgium

Testosterone (T) increases brain aromatase activity (AA) and this enzymatic induction appears to be a limiting step in the activation of copulatory behaviour by T (Balthazart et al., 199Oa). We recently demonstrated (Balthazart et al., 1990b) that T increases the number of aromatase-immunoreactive (ARO-ir) cells in the quail preoptic area (POA). However, which T metabolites are involved and the possibility of anatomical specificity for these effects were not yet clear. In Experiment 1, we disassociated the effects of androgens and estrogens on aromatase induction by comparing ARO-ir in neurons of quail treated with T alone (which activated copulation) or T in the presence of a potent aromatase inhibitor, R76713 (which depressed AA levels and suppressed T-activated copulatory behavior). T increased the number of ARO-ir cells in POA, bed nucleus striae terminalis (BNST) and tuberal hypothalamus (TU). The T effect was inhibited by concurrent treatment with aromatase inhibitor in TU, but not in POA and BNST. In Experiment male quail received silastic implants filled with either T, or its androgenic Sa-dihydrotestosterone (DHT) or its estrogenic metabolite, estradiol-17p (E2) combined metabolites (DHT + E2). High levels of male sexual behavior were

2, castrated metabolite, or with the activated by

T and by the DHT + E2 treatment. Moderate effects only were observed in birds that received DHT or E2 alone. Both in POM and TU, the treatment with either T or DHT + E2 produced a major increase in the number of labeled cells. DHT alone had no significant effect at this level while E2 alone only had limited effects that did not always reach significance. The increase observed in DHT + E2 birds always had a larger magnitude than in E2 birds but this difference only reached significance in the TU and not in the POM. These data confirm the existence of a synergism between androgenic and estrogenic