Merle E. Meyer

Sex differences in locomotor activity after acute and chronic cocaine administration.

Adult, intact and gonadectomized male and female Wistar rats (n = 9) were exposed to an automated open field to assess the behavioral effects of acute cocaine administration (saline, 1.0 and 10.0 mg/kg subcutaneous). The subjects were exposed to the open field for 10 min, removed to be injected and returned to the open field for another 30 min. Three saline and two drug sessions were run in counterbalanced order. Locomotor activity in intact and castrated male rats and ovariectomized female rats decreased following injection, irrespective of the dose of cocaine. The locomotor activity of intact female rats was higher than that of any other group of subjects. It decreased during the session after saline and 1.0 mg/kg cocaine, but increased towards the end of the 30 min session after 10.0 mg/kg. Rearing measures paralleled the observations on locomotor activity. To determine the effects of chronic, home-cage, cocaine administration, five of the subjects in each group were injected with 10.0 mg/kg cocaine for 9 consecutive days. The remaining four subjects received saline injections. On day 10, all subjects were re-exposed to the open-field for 10 min, removed, injected with 10.0 mg/kg cocaine and returned to the open field for another 30 min. Chronic home cage cocaine administration produced an increase in cocaines effects on locomotor activity and rearing in intact female rats only. However, behavioral sensitization was also observed in intact female rats who had been treated with saline for 9 consecutive days, suggesting that behavioral sensitization to cocaine in intact female rats may develop very rapidly and independent of environmental context.

Tonic immobility and the dorsal immobility response in twelve species of muroid rodents

Two behavioral inhibitory responses, tonic immobility and the dorsal immobility response, were studied in 12 species of rodents. The duration and number of positive trials of tonic immobility were found to be correlated with the duration of the dorsal immobility response across species. These observations, along with the behavioral similarity of these two responses (e.g., rigid immobile posture, tremor) support the suggestion that tonic immobility and the dorsal immobility response be considered as members of a general class of complex behavioral inhibitory responses that are mediated by a common neural substrate. Although there is no reason to suspect gross differences in cortical development or function across the species in this study, large differences were apparent in various measures of the immobility responses studied. These results do not appear to support the hypothesis of an inverse relation between “phylogenetic rank” and susceptibility to immobility. Peromyscus species were found to exhibit longer durations of immobility than Microtus species. In light of earlier observations on predators, and the failure of Onychomys leucogaster (a predatory mouse) to exhibit tonic immobility in the present study, it was suggested that predatory species may be less susceptible to immobility responses than other species.

Dopamine D1 receptor family agonists, SK&F38393, SK&F77434, and SK&F82958, Differentially affect locomotor activities in rats

Dopamine D1 receptor family agonists, 2,3,4,5,-tetrahydro-7,8-dihydroxy-1phenyl-1H-3-benzazepine (SK&F38393), 3-allyl-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SK&F77434), and 3-allyl-6-chloro-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazep ine (SK&F82958), were compared for their behavioral effects on horizontal movement time, rearing time, stereotypy time, and thigmotaxis time. All agonists resulted in biphasic effects with attenuation followed by potentiation (0.01-10.0 mg/kg, SC). While SK&F38393 did not potentiate horizontal movement and rearing times, and had minor effects on thigmotaxis, SK&F77434 and SK&F82958 potentiated horizontal movement and rearing behaviors and attenuated thigmotaxis. The results were discussed in terms of the binding characteristics and current receptor theory.

Effects of intracerebral quinpirole on locomotion in rats

The effects of the dopamine D2 receptor agonist quinpirole (LY 171555) on locomotor activity and margin time (thigmotaxis or wall-hugging) were measured for 2 h in rats injected either s.c. (vehicle, 0.02, 2.0 mg/kg) or directly into either the dorsal striatum or nucleus accumbens (vehicle, 0.1, 1.0, 10, 20 or 40 micrograms bilaterally in each site). In all groups, margin time decreased as drug dose increased. As in previous research, quinpirole given s.c. decreased locomotor activity at a low dose and had a biphasic effect on locomotor activity at the high dose. Both of these effects were also elicited by quinpirole injected directly into the dorsal striatum; 10 and 20 micrograms decreased locomotion immediately, while 40 micrograms led to both the immediate decrease and a later increase. In contrast, the lowest doses of quinpirole (0.1 and 1.0 microgram) injected into the nucleus accumbens led to an increase in locomotion from 20 to 60 min, while the higher doses led only to the early decrease. Thus, both the locomotor activating and inhibiting effects of quinpirole are found in both the nucleus accumbens and the dorsal striatum, but the differing dose-response relationships indicate that the mechanisms are not the same in these two brain regions.

Behavioral effects of opioid peptide agonists DAMGO, DPDPE, and DAKLI on locomotor activities

The effects of the mu-selective agonist DAMGO (ICV doses of 0.00, 0.01, 0.1, or 1.0 micrograms), the delta-selective agonist DPDPE (ICV doses of 0.00, 0.1, 1.0, or 10.0 micrograms), and the kappa-selective agonist DAKLI (ICV doses of 0.00, 0.01, 0.1, or 1.0 micrograms) were tested in rats for 60 min in an activity monitor. The durations in seconds of linear locomotor time, rearing time, stereotypy time, and margin time (thigmotaxis) were measured during six 10-min time blocks. DAMGO (0.1 and 1.0 micrograms) resulted in biphasic effects, inhibition followed by hyperactivity for linear locomotor, rearing, and stereotypy times, and an inhibition of thigmotaxis. DPDPE (10.0 micrograms) was associated with monophasic potentiation of linear locomotor activity and mixed effects in stereotypy times. DAKLI did not effect horizontal, rearing, or margin times; only stereotypy times resulted in mixed effects of DAKLI. The differential behavioral profiles were discussed in reference to the three opioid receptor subtypes.

Behavioral effects of long-term administration of an anabolic steroid in intact and castrated male Wistar rats.

Once a week, intact and castrated male Wistar rats were intramuscularly injected with a 0.2 ml suspension of either 0, 10, or 50 mg nandrolone decanoate in cottonseed oil, for 8 consecutive weeks. After the sixth injection, locomotor activity was measured in an open-field and the acquisition of lever press behavior was assessed in an autoshaping procedure. Subsequently, all subjects were exposed to four sessions of continuous reinforcement prior to one session in which the effects of steroid administration on extinction were assessed. Locomotor activity decreased for all groups of rats with continued exposure to the open-field, differences between groups were not observed. Rats treated with the highest dose of nandrolone decanoate spent more time in the margin of the open-field. There were no significant differences between groups on any of the learning measures. Long-term, high-dose steroid administration in conjunction with mild food deprivation inhibited growth in intact and castrated rats, while low dose administration affected body weight in intact rats only. Steroid administration resulted in heavier and enlarged kidneys and lighter testes as well. These results suggest that the administration of anabolic steroids not only produces observable physiological changes, but that it may also affect spontaneous behavior. The failure to find differences in learning indices may have been a function of the particular paradigms used in the present experiment.

Ontogeny of biphasic locomotor effects of quinpirole

The effects of the dopamine D2/D3 receptor agonist quinpirole (LY171555) on locomotor activity were tested on rats of 10, 15, 20, 30, and 60 days of age. In two separate experiments, doses of 0 (vehicle), 0.02, 0.2, or 2.0 mg/kg quinpirole were injected SC into rats at each age, and their effects measured either for 2 h at 15-min intervals, or 30 min at 5-min intervals. At 10, 15, and 20 days of age, quinpirole significantly increased distance travelled in a dose-dependent manner. At 30 and 60 days of age, quinpirole significantly decreased distance travelled early in the session and increased it later. These results suggest that a dopamine autoreceptor begins to function between 20 and 30 days of age. Concomitant with the appearance of quinpirole-induced locomotor suppression early in the session, the amount of quinpirole-induced activation late in the session declined.

Effects of dopamine D1 antagonists SCH23390 and SK&F83566 on locomotor activities in rats

The effects of the dopamine D1 antagonists R-(+)-7-chloro-8-hydroxy-3-methyl-1phenyl-2,3,4,5-tetrahydro-1-H-3 -benzazapine (SCH23390) and (+-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1- H-3-benzazapine (SK&F83566) were tested for 2 h on linear locomotor, rearing, stereotypy, and margin times in an open field. Each of the antagonists attenuated the duration of linear locomotion, rearing, and stereotypy times in a dose- and time-dependent manner. The effectiveness of the antagonists was relatively brief and SCH23390 was more effective than SK&F83566 on each behavior. The two antagonists had differential effects on margin time.

Effects of intraaccumbens dopamine agonist SK&F38393 and antagonist SCH23390 on locomotor activities in rats.

The present study examined the effects of the dopamine D1 and D5 subtype receptors agonist, R(+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SK&F38393), and antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-ben zaz epine (SCH23390), on locomotor activities after bilateral microinjection into the nucleus accumbens (Acb). SK&F38393 (0.1-10.0 micrograms) significantly potentiated and SCH23390 (0.01-1.0 microgram) significantly attenuated locomotor activity as measured by horizontal distance in cm. The data were supportive of the hypothesis that dose-related locomotor activities induced by microinjections of SK&F38393 into the Acb are independently mediated by D1 and D5 subtype receptors.

Affiliative behavior in voles: Effects of morphine, naloxone, and cross-fostering

Species differences in affiliative behavior were examined in prairie and montane voles. Unfamiliar male-female pairs were placed in a test-cage for 2 hr and side-by-side huddling was recorded during the third hour. Prairie vole pairs spent a mean of 31.2 minutes in contact whereas montane voles were in contact only 1.3 minutes. In order to examine the effects of experience on affiliative differences, pups of each species were cross-fostered. Fostered prairie vole parents did not survive longer than 7 days, whereas fostered montane voles were successfully weaned; cross-fostering had no effect on their huddling behavior when tested as adults. The effects of morphine (5 and 10 mg/kg) and naloxone (5 and 10 mg/kg) on side-by-side contact were evaluated in both species. Morphine (10 mg/kg) reduced huddling duration and activity levels in prairie voles. There were no other drug effects in either species.