Individual differences in rats' reactivity to novelty and the unconditioned and conditioned locomotor effects of methamphetamine

Rat's reactivity to inescapable novelty can predict the subsequent psychomotor effects of many stimulants. This relation has not been examined for methamphetamine. Experiment 1 assessed the locomotor effects of methamphetamine (0.0625-1.0 mg/kg). On average, acute administration of methamphetamine (0.25, 0.5, and 1 mg/kg) had a stimulant effect on activity; locomotor sensitization was seen after repeated administration of 0.5 and 1 mg/kg. In a subsequent drug-free test, rats that had the locomotor chamber paired with 0.25, 0.5, or 1 mg/kg methamphetamine on eight separate occasions were more active than controls--conditioned hyperactivity. Experiment 2 used the 0.5-mg/kg dose to examine whether forced novelty exposure (novelty-induced activity) or free-choice novelty (approach to novel environment or object interaction) was predictive of methamphetamine's psychomotor effects. Only reactivity to inescapable novelty was systematically correlated with methamphetamine-induced activity. Rats more reactive to novelty [high responders (HR)] were more active to the acute and chronic methamphetamine challenge. Furthermore, these HR showed more conditioned hyperactivity than low responders (LR). Although acute methamphetamine did not have a stimulant effect in LR, only the LR displayed locomotor sensitization after chronic methamphetamine. This research extends the predictive variable of reactivity to inescapable novelty to methamphetamine's conditioned and unconditioned locomotor effects.     

Clonidine and yohimbine modulate the effects of naloxone on novelty-induced hypoalgesia

Previous research has shown that repeated daily pretreatment with the opiate receptor blocker naloxone retards the development of habituation to novelty-induced hypoalgesia. The present experiments were conducted in order to determine whether noradrenergic substrates mediate this effect. Animals in the NAL condition were administered 10 mg/kg naloxone prior to assessment of pain sensitivity on a 48.5° C hot plate. Control animals (SAL condition) were administered saline prior to pain assessment, and naloxone 2–4 h later. Paw lick latencies declined over repeated tests in SAL animals, suggesting the habituation of novelty hypoalgesia. Naloxone pretreatment attenuated this decline. The longer paw lick latencies observed in NAL condition animals were reduced by administration of 2 µg/kg clonidine, a specific noradrenergic alpha-2 receptor agonist, and enhanced in a dose dependent (0.5–4.0 mg/kg) fashion by the alpha-2 antagonist yohimbine. Clonidine and yohimbine either failed to alter pain reactivity in control animals, or produced less marked effects than those observed in naloxone-exposed animals. These results suggest that noradrenergic substrates mediate naloxone's effects on novelty hypoalgesia.     

Naloxone administration following brief exposure to novelty reduces activity and rearing in mice upon 24-h retest: A conditioned aversion?

It has recently been reported that naloxone treatment, prior to initial exposure to a novel arena, results in significant behavioural change when animals are retested 24 h later. In an attempt to clarify the nature of this delayed action of the opiate antagonist, three further studies have been performed. In the first experiment, male mice were injected with naloxone hydrochloride (0–10 mg/kg, IP) immediately after their initial experience of the test arena. When retested 24 h later, all groups that had previously received naloxone exhibited greatly reduced activity and rearing, with no evidence of a dose-response relationship. In the second experiment, naloxone (0–10 mg/kg) failed to induce a conditioned place aversion when administered according to the above regimen. In the final experiment, no evidence for a naloxone-induced taste aversion to saccharin was observed. It is concluded that the behavioural changes observed in the open-field study may reflect either (a) subtle aversive properties of naloxone which are insensitive to traditional one-trial paradigms or (b) opioid modulation of memory for non-painful experiences.     

Effects of chlordiazepoxide and imipramine on maze patrolling within two different maze configurations by psychogenetically selected lines of rats

Male rats of two lines of rats psychogenetically selected and bred for extremes in performance in shuttle box avoidance received an acute IP injection of chlordiazepoxide (CDP; 2.5, 5.0, 10.0 mg/kg), imipramine HCl (IMI; 0.33, 1.0, or 3.0 mg/kg), or vehicle. The rats were placed, 35 min after injection, in an enclosed maze with either a simple configuration with an unilluminated central arena or a complex configuration with a brightly illuminated central arena, and spontaneous maze patrolling was evaluated. Total locomotor activity during the 6-min maze test was significantly reduced by 5–10 mg/kg CDP for both RHA/Verh and RLA/Verh lines of rats in both the simple and the complex maze configurations. Treatment with 10 mg/kg CDP reduced the total explored area for both rat lines in both maze configurations. In addition, the maze area explored by RHA/Verh rats was also reduced by 5.0 mg/kg CDP for the simple configuration and by 2.5 and 5.0 mg/kg CDP for the complex configuration. Entry into the unilluminated central field of the simple maze was reduced by 5–10 mg/kg CDP only in RHA/Verh rats. In contrast, 2.5 mg/kg CDP significantly increased entry into the brightly illuminated central arena of the complex maze for the RLA/Verh rats. The doses of IMI used were without effect on the parameters of maze patrolling behavior evaluated, with the single exception that the locomotor activity of RHA/Verh rats tested in the simple maze configuration was decreased by 3.0 mg/kg IMI. The results indicate that, although the effects of CDP were generally similar for total activity and the area explored in the two psychogenetic lines investigated, there was a qualitative difference in its effect on entry into an illuminated arena.     

Atypical anxiolytic-like response to naloxone in benzodiazepine-resistant 129S2/SvHsd mice: role of opioid receptor subtypes

Rationale Mice of many 129 substrains respond to environmental novelty with behavioural suppression and high levels of anxiety-like behaviour. Although resistant to conventional anxiolytics, this behavioural phenotype may involve stress-induced release of endogenous opioids.Objectives To assess the effects of opioid receptor blockade on behavioural reactions to novelty stress in a chlordiazepoxide-resistant 129 substrain.Materials and methods Experiment 1 contrasted the effects of the broad-spectrum opioid receptor antagonist naloxone (1.0–10.0 mg/kg) in C57BL/6JOlaHsd and 129S2/SvHsd mice exposed to the elevated plus-maze. Experiments 2–4 examined the responses of 129S2/SvHsd mice to the μ-selective opioid receptor antagonist β-funaltrexamine (2.5–10.0 mg/kg), the δ-selective antagonist naltrindole (2.5–10.0 mg/kg) and the κ-selective antagonist nor-binaltorphimine (2.5–5.0 mg/kg).Results 129 mice displayed higher levels of anxiety-like behaviour and lower levels of general exploration relative to their C57 counterparts. Although naloxone failed to alter the behaviour of C57 mice, both doses of this antagonist produced behaviourally selective reductions in open-arm avoidance in 129 mice. Surprisingly, none of the more selective opioid receptor antagonists replicated this effect of naloxone: β-funaltrexamine was devoid of behavioural activity, naltrindole suppressed rearing (all doses) and increased immobility (10 mg/kg), while nor-binaltorphimine (5 mg/kg) nonspecifically increased percent open arm entries.Conclusions Recent evidence suggests differential involvement of opioid receptor subtypes in the anxiolytic efficacy of diverse compounds including conventional benzodiazepines. The insensitivity of 129 mice to the anxiolytic action of chlordiazepoxide, coupled with their atypical anxiolytic response to naloxone (but not more selective opioid receptor antagonists), suggests an abnormality in anxiety-related neurocircuitry involving opioid-GABA interactions.     

Morphine-induced hyperactivity in rats — a rebound effect?

Summary The behavioural nature of the delayed hyperactivity induced by systemic administration of morphine was studied in rats. Different components of motility induced by morphine with or without naloxone or haloperidol at different times were analyzed by observation and quantified by an Opto Varimex-3 Activity Meter. By this automatic recording system motility was discriminated into horizontal and two different vertical components and the total distance run by each of the rats was quantified by a computer program. Simultaneously the running pattern was recorded by a XY plotter. By means of these recordings, three subsequent phases of behaviour could be recorded after morphine (15 mg/kg i.p.): 1. a depressed phase (akinesia) lasting 1.5–2 h, followed, 2. by an intermediate phase for 1–1.5 h, still dominated by akinesia but interrupted by sudden bursts of hyperactivity. Finally, 3. a hyperactivity phase lasted for 1.5–2 h, characterized by an equal enhancement of locomotor activity and stereotypy. After 30 mg/kg of morphine the hyperactivity was predominantly characterized by locomotor activity and stereotypy and rearing were less prominent than after the smaller dose. Naloxone (2 mg/kg i.p.) given at the beginning of the hyperactivity phase significantly antagonized rearing but not other motility parameters. However, coadministration of naloxone (2 mg/kg i.p.) simultaneously with morphine (15 mg/kg) clearly antagonized akinesia and completely prevented the development of the delayed hyperactivity. Haloperidol (0.2 mg/kg i.p.) at the beginning of the hyperactivity phase clearly antagonized all of the motility parameters seen during this phase.We conclude 1. that stereotypy and locomotor activity of the hyperactivity phase produced by morphine are not strictly combined since they follow different dose dependencies: locomotor activity increased more after the higher dose of morphine, however, stereotypy and rearing did not. 2. Akinesia and hyperactivity phase might both be triggered by an initial activation of opioid receptors immediately after injection of morphine. However, the hyperactivity phase (being dopamine dependent in all components measured) seems to develop to an opioid receptor independent process as during the hyperactivity phase it can be reversed by haloperidol but not by naloxone anymore.Correspondence to U. Havemann-Reinecke at the above address     

Effect of naloxone on the behaviour of rats exposed to a novel environment

It has recently been suggested that endogenous opiates may play a general role in stress responding. To test this hypothesis, naloxone hydrochloride (0.5–4.0 mg/kg SC) was administered to rats exposed to an open field situation. Naloxone treatment produced a decrease in locomotor activity and rearing, and an increase in defaecation. A simple dose-response relationship was not observed, with the most potent effects exerted by the 1 mg/kg dose. Nevertheless, these results indicate that naloxone increases emotionality in the rat and suggest that opioid peptides may be released under conditions of nonpainful stress.     

Nucleus accumbens opiate-dopamine interactions and locomotor activation in the rat: evidence for a pre-synaptic locus

Locomotor activation produced by the indirect dopamine (DA) agonist amphetamine is reversed by the opiate-receptor antagonist naloxone. Since amphetamine-stimulated locomotion results from the release of DA within the nucleus accumbens (N.Acc.), it is possible that these effects of naloxone result either from a decrease in the pre-synaptic release of DA within the N.Acc. or from a disruption of the effects of DA at, or distal to, the post-synaptic DA receptor. In the present study, we investigated the effects of naloxone on the locomotor-activating properties of dopamine injected directly into the nucleus accumbens. Naloxone (0-2 mg/kg) had no significant effect of DA-stimulated locomotion; the lowest dose of naloxone tested (0.5 mg/kg) was shown to significantly disrupt the locomotor activation produced by amphetamine (0.5 mg/kg). In separate animals, very high doses of naloxone (5.0 mg/kg) had no significant effect on locomotor activation produced by the DA receptor agonist apomorphine in rats following 6-hydroxydopamine (6OHDA) denervation of the N.Acc. These results indicate that naloxone must disrupt amphetamine-stimulated locomotion through its action presynaptic to N.Acc. DA receptors.     

Effects of naloxone on morphine induced sedation and hyperactivity in the hamster

Three experiments investigated the effects of naloxone on morphine elicited changes in hamster locomotor activity. In Experiment 1, a prior subcutaneous injection of naloxone (0.4 mg/kg) converted morphine (15 mg/kg) elicited hypoactivity into hyperactivity: Compared with saline controls, naloxone pretreated animals were hyperactive following a subcutaneous injection of morphine. Experiment 2 investigated the effects of four doses of naloxone (0, 0.04, 0.1, 0.4 mg/kg) on morphine elicited hyperactivity. Results indicated that naloxone reversal of morphine elicited hyperactivity is directly related to dose of naloxone. In Experiment 3, naloxone (0.4 mg/kg) was administered one and two hours after a morphine injection. Compared with saline controls, morphine treated animals were hypoactive for approximately 40 minutes after each of the naloxone injections. Results are discussed in terms of a modified dual-action hypothesis.     

The 5-HT1A receptor and behavioral stimulation in the rat: effects of 8-OHDPAT on spontaneous and cocaine-induced behavior

Rationale The contribution of the 5-HT_1A somato-dendritic autoreceptor populations to spontaneous and cocaine-induced locomotion is unclear.Objectives To use a low dose range of ±8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) to preferentially stimulate 5-HT_1A autoreceptors and a medium 8-OHDPAT dose range to stimulate both 5-HT_1A autoreceptors and postsynaptic receptors as pretreatments prior to either saline or cocaine.Methods In experiment 1, either a medium dose of 8-OHDPAT (0.4 mg/kg) or a low dose (0.05 mg/kg) was given as pretreatments 20 min before five separate 20-min open-field tests. In experiment 2, the pretreatments were changed to a low dose range of 8-OHDPAT (0.01–0.05 mg/kg), with or without WAY 100635 (0.01–0.05 mg/kg). In experiment 3, the 8-OHDPAT pretreatments (0.01, 0.025 or 0.05 mg/kg) were administered 20 min prior to saline or cocaine (10 mg/kg) tests. In experiment 4, a medium dose range (0.2–0.3 mg/kg) was given 20 min prior to saline or cocaine (10 mg/kg) tests.Results Experiment 1 showed that 8-OHDPAT (0.4 mg/kg) tended to increase locomotor activity but that pretreatment with 0.05 mg/kg severely suppressed locomotor activity. In experiment 2, 8-OHDPAT in the low dose range inhibited locomotor activity and this effect was reversed by co-administration of WAY 100635. Experiment 3 showed that the low-dose 8-OHDPAT pretreatment reduced locomotor activity in saline but not cocaine tests. In experiment 4, 8-OHDPAT in the medium dose range enhanced locomotor activity in cocaine tests.Conclusions It is suggested that the facilitatory effect of 8-OHDPAT on cocaine-induced locomotor stimulation is mediated by inhibition of 5-HT_1A somato-dendritic autoreceptors.     

Functional behavioral homology between rat 5-HT1B and guinea pig 5-HT1D receptors in the modulation of prepulse inhibition of startle

The serotonin (5-HT) 1B receptor in rats and mice appears to be homologous to the 5-HT_1D receptor found in other mammals, such as guinea pigs and humans. The present series of experiments explored the functional similarity between the rat 5-HT_1B receptor and the guinea pig 5-HT_1D receptor on two behavioral measures known to be influenced by 5-HT_1B receptor manipulations in rats: prepulse inhibition of the startle response (PPI) and locomotor activity. Because the 5-HT_1B agonist RU 24969 disrupts PPI and stimulates locomotor behavior in rats, it was predicted that the 5-HT_1D agonist, SDZ 219–964, would demonstrate a similar behavioral profile in guinea pigs. In support of this hypothesis, SDZ 219–964 was found to disrupt PPI dose-dependently (1.0 and 2.0 mg/kg) without significantly affecting startle amplitude and to increase locomotor activity (0.5–2.0 mg/kg) in guinea pigs. In guinea pigs, RU 24969 failed to affect PPI, although it did increase locomotor activity, indicating that RU 24969 may have activity at the 5-HT_1D receptor. As expected, RU 24969 in rats disrupted PPI (2.5 and 5.0 mg/kg) and significantly increased locomotor activity (1.25–5.0 mg/kg). In rats, however, SDZ 219–964 had generalized, stimulatory effects on startle reactivity, without independent effects on PPI or locomotor activity. The spatial patterns of locomotion exhibited by guinea pigs treated with SDZ 219–964 versus those of rats treated with RU 24969 demonstrate important qualitative differences in structure, indicating that the neural substrates subserving these effects may be different. It is concluded that a functional similarity exists between 5-HT_1D and 5-HT_1B receptors with regard to the modulation of sensorimotor inhibition and, to a lesser extent, locomotor activity.     

Evidence for multiple opiate receptor involvement in different phencyclidine-induced unconditioned behaviors in rats

Rats were used for comparing the behavioral response profiles of phencyclidine (PCP) and d,1-N-allylnormetazocine (NANM), two drugs that are proposed to exert their effects through the PCP/sigma receptor. Phencyclidine (1.0–5.0 mg/kg) and NANM (2.5–10.0 mg/kg) induced dose-related increases in locomotion, sniffing, repetitive head movements, non-object directed mouth movements, and ataxia. Both drugs also increased food and water consumption during the latter portion of the drug response. Ingestive behaviors induced by PCP (2.5 mg/kg), as with eating and drinking stimulated by the mu-opiate morphine (2.0 mg/kg), were blocked by a relatively low dose of the opiate antagonist naloxone (0.5 mg/kg). Multiple injections of PCP (2.5 mg/kg for 4 days) or NANM (10.0 mg/kg for 4 days) augmented several measures of behavioral activation, including horizontal locomotion, rearing, and nonfocused sniffing, but did not significantly change stereotyped behaviors or ataxia. Reciprocal cross-sensitization of locomotor activation is indicated by the finding that the response to a challenge injection of PCP (2.5 mg/kg) or to NANM (10.0 mg/kg) after 4 days of treatment with the other drug closely resembled the enhanced locomotor response observed after the chronic treatment. Phencyclidine and NANM thus appear to exert many of their effects on unconditioned behavior through common mechanisms, including interaction with sigma receptors. In addition, these findings are consistent with previous suggestions that a muopiate receptor system may modulate some effects of PCP.     

Memory facilitation by naloxone is due to release of dopaminergic and beta-adrenergic systems from tonic inhibition

The post-training IP administration of naloxone (0.8 mg/kg) facilitates memory consolidation of the habituation of a rearing response to a tone in rats. Amphetamine (1.0–2.5 mg/kg or nicotine (0.2–0.5 mg/kg), and amphetamine (2.5 mg/kg) plus nicotine (0.5 mg/kg) have no effect. The higher doses of amphetamine or nicotine, however, when given together with a dose of naloxone which is ineffective alone (0.2 mg/kg), markedly enhance consolidation. Haloperidol (0.5 mg/kg), propranolol (0.5 mg/kg), and phenoxybenzamine (2.0 mg/kg) have no effect on their own; whereas tolazoline (2.0 mg/kg) impairs consolidation. The effect of naloxone (0.8 mg/kg) is antagonized by haloperidol and by propranolol, but not by phenoxybenzamine or tolazoline. The results suggest that naloxone causes memory facilitation through the release of central dopaminergic and beta-adrenergic mechanisms from a tonic inhibitory influence of endogenous opiate peptide systems.     

Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze

Rationale Although 5-HT₂ receptors seem to play an important role in anxiety, results from numerous studies are still highly variable. Moreover, little is known about the behavioral effects of centrally administered 5-HT₂ compounds in animal models of anxiety. Objective The current study was performed to: (1) further investigate the effects of 5-HT₂ receptor activation in rats exposed to the elevated plus-maze (EPM) and the open-field arena, two widely used animal models for studying anxiety and locomotor activity; and (2) evaluate the involvement of the 5-HT₂ receptors within the basolateral nucleus of the amygdala (BLA) in the modulation of such effects. Methods In the first experiment, male Wistar rats were exposed for 5 min to the EPM 27 min following intraperitoneal (i.p.) (1.0 ml/kg) injections of the preferential 5-HT_2C receptor agonist 6-chloro-2[1-piperazinyl]pyrazine (MK-212) at doses of 1.0, 2.0, or 4.0 mg/kg. Control animals were injected with saline. The percentage of open-arm entries and the percentage of time spent in these arms were employed as anxiety indexes, whereas the number of closed-arm entries was calculated as indicative of locomotor activity. In the second experiment, rats were exposed for 10 min in an open-field arena to further assess the interference of the same MK-212 doses upon locomotor activity. In Experiment 3, rats were microinjected (0.2 μl) either with the mixed 5-HT_2A/2C receptor antagonist ritanserin (0.5, 1.25, 2.5, and 5.0 μg) or its vehicle into the BLA 12 min following i.p. injections of saline or the intermediate dose of MK-212 (2.0 mg/kg). Fifteen minutes later, each animal was exposed to the EPM as before. Results Whereas the highest dose of MK-212 (4.0 mg/kg) induced motor-suppressant effects in both EPM and open-field arena, the intermediate dose of the drug (2.0 mg/kg) reduced open-arm exploration without significantly affecting the number of closed-arm entries. This behavioral profile, consistent with selective anxiogenic effect in the EPM, was dose-dependently prevented by ritanserin microinfusion into the BLA. In saline-pretreated animals, however, ritanserin (all doses) was ineffective. Conclusions MK-212 increases anxiety and decreases locomotor activity. The anxiogenic-like profile of 5-HT₂ receptor activation is prevented by the blockade of 5-HT₂ receptors within the BLA, which does not have an effect by itself upon basal anxiety levels triggered by the EPM.     

Ontogenesis of morphine-induced behavior in the rat

Ten, seventeen and twenty-four day old rats were observed using a behavioral-time sampling procedure following injection of saline, 0.1, 0.5, 1.0 or 5.0 mg/kg/5cc morphine sulphate. At Day 10, the predominant response to morphine was a depression of locomotor activity. At the 5 mg/kg dose, catalepsy was also seen. In animals of this age, 0.1 mg/kg morphine, which was not sufficient to depress activity, also had no effect on stereotyped gnawing/mouthing behavior, nor did it produce any increase in locomotor activity. A morphine-induced increase in locomotion was first seen on Day 17 (after 0.5 mg/kg morphine). As with Day 10 animals, Day 17 animals given 5 mg/kg morphine showed a depression of locomotion and catalepsy. Stereotypic gnawing/mouthing behavior was first seen in Day 24 animals (after 5 mg/kg morphine), although no dose of morphine produced significant differences in activity at this age. Possible mechanisms resulting in these marked alterations in behavioral response patterns to morphine during this two week period of ontogeny are discussed.     

Behavioral effects of profadol in the rat

The effects of profadol, an analgesic with mixed agonist and antagonist properties, were evaluated on continuous avoidance responding and locomotor activity in the rat. Profadol was tested alone and concomitantly with 8.0 mg/kg of naloxone. Profadol had a biphasic effect on avoidance response rate, increasing it at from 0.5–8.0 mg/kg and decreasing it at 32 mg/kg. Naloxone blocked both the rate increasing and the rate decreasing effects of profadol on avoidance responding. Locomotor activity was unaffected by 0.5–64 mg/kg of profadol alone, but was increased when profadol and naloxone were administered together. These findings extend the dual action hypothesis for morphine to a partial morphine agonist. This study provides further evidence that the behavioral activity of narcotic antagonists can be evaluated in the rat in an objective and quantitative manner.Publication No. 1171 of the Division of Basic Health Sciences of Emory University. This investigation was supported by USPHS Grant MH 21699.     

Methylphenidate potentiates morphine-induced antinociception, hyperthermia, and locomotor activity in young adult rats

The goal of this study was to determine if the exaggerated morphine-induced conditioned place preference (CPP) response seen in adult rats after preweanling methylphenidate exposure is unique to reward-mediated behaviors or is indicative of generalized changes in opioid-mediated behaviors. Rats were exposed to saline or methylphenidate (2.0 or 5.0 mg/kg) for 10 consecutive days starting on postnatal (PD) 11 with testing beginning on PD 60. In Experiment 1, morphine-induced (0, 2.5, 5.0 or 10.0 mg/kg) antinociception was assessed using the tail immersion and hot plate tasks. In Experiment 2, morphine-induced (0, 2.5, 5.0, or 10.0 mg/kg) hyperthermia and locomotor activity were measured. Morphine caused an increase in antinociception, with early methylphenidate (5.0 mg/kg) exposure potentiating the effects of 5.0 mg/kg morphine. Rectal temperatures were elevated after morphine, with the greatest increase occurring in male rats. Methylphenidate potentiated the hyperthermic effects of morphine (10.0 mg/kg) but only in males. Moderate doses (2.5 and 5.0 mg/kg) of morphine increased the locomotor activity of adult rats, while a higher dose (10.0 mg/kg) decreased locomotion. Interestingly, methylphenidate-pretreated females showed increased locomotor activity relative to controls. These results suggest that early methylphenidate exposure induces general changes in opioid system functioning that are not specific to reward-mediated behaviors.     

Effects of U50,488H on locomotor activity in the hamster

Two experiments investigated the effects of the specific kappa opiate agonist, U50,488 on locomotor activity in the golden Syrian hamster. In Experiment 1, the effects of U50,488 were found to be dose-related, with a 1 mg/kg dose eliciting hyperactivity and a 10 mg/kg dose eliciting hypoactivity. In Experiment 2, the dual effects of U50,488 on locomotor activity were shown to be naloxone (1 mg/kg) reversible. It is suggested that the effects of U50,488 on activity are consistent with the reported dual opposing influences of kappa agonists in the substantia nigra pars compacta and pars reticulata.     

Morphine,d-Pen2,d-Pen5 enkephalin and U50,488H differentially affect the locomotor activity and behaviours induced by quinpirole in guinea-pigs

The effects of morphined-Pen²,d-Pen⁵ enkephalin (DPDPE) and U50,488H on the behavioural syndrome elicited by the dopamine (DA) D-2 agonist quinpirole, were investigated. Morphine (1, 5 and 15 mg/kg SC) and morphine administered intracerebroventricularly (ICV) (2×5 µl, 10^–3 M; total dose = 10 nmol) produced piloerection and sedation. DPDPE-ICV (2×5 µl and 2×10 µl, 10–³ M; total doses = 10 and 20 nmol) produced piloerection and sedation similar to morphine. U50,488H (1 mg/kg SC) induced locomotor activity and some stereotyped behaviour, whereas U50,488H (5 and 10 mg/kg SC) induced muscle rigidity and dystonic-like movements. The locomotor and behavioural response elicited by quinpirole (3 mg/kg IP) was attenuated in guinea-pigs pretreated with morphine (1, 5 and 15 mg/kg SC), morphine-ICV (2 × 5 µl, 10–³ M), and DPDPE-ICV (2 × 5 µl and 2 × 10 µl, 10^–3 M). These effects were reversed by naloxone (15 mg/kg SC). U50,488H (1 mg/kg SC) increased the quinpirole-induced locomotor activity, whereas U50,488H (5 and 10 mg/kg SC) decreased the locomotor activity and stereotyped behaviours produced by quinpirole. These results indicate that the gross behavioural effects of mu, delta and kappa opioids differ in guinea-pigs compared to other rodent species, and suggest differential involvement of these opioid receptor subtypes with DA D-2 receptor-mediated activity.     

Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in nijmegen wistar rats

The aim of the study was to investigate the biphasic locomotor response to ethanol in rats. Based on the recent finding that high responders to novelty (HR) and low responders to novelty (LR), selected from an outbred Nijmegen Wistar rat population, show differences in ethanol intake and preference, it was initially investigated to what extent HR and LR differ in their locomotor response to ethanol. A dose-response curve (0.2–2.0 g/kg, IP) was established using standardized activity boxes. HR showed a significant increase at 0.5 g/kg, followed by a significant decrease at doses 1.0–2.0 g/kg; LR showed only a decrease at doses 1.0–2.0 g/kg. Secondly, it was investigated to what extent stress altered the ethanol-induced increase and decrease, respectively. For that purpose, the ethanol-induced locomotor effects (0.5 and 1.0 g/kg) were analyzed in habituated and non-habituated (stressed) HR and LR; habituation consisted of a 15-min adaptation period to the activity cages. Stress significantly enhanced the excitatory effects in HR, but had no effect on the sedative effects in HR and LR. Finally, the locomotor effects of sub-chronic treatment (7 days) with an excitatory (0.5 g/kg) or sedative (1.0 g/kg) dose were analyzed in HR and LR. The excitatory effect of 0.5 g/kg disappeared throughout the treatment in HR, whereas the sedative effects of 1.0 g/kg remained the same in HR and LR. It is concluded that the mechanism underlying the ethanol-induced motor excitation differs completely from that underlying the ethanol-induced sedation. Given the known differences in the make-up of the brain and endocrine system between HR and LR, these animals are suggested to be good models for studying the mechanisms underlying the biphasic locomotor response to ethanol in rats.