Spontaneous Motor Activity In Rats Research Articles

Prazosin attenuates the effects of cocaine on motor activity but not on schedule-controlled behavior in the rat

The spontaneous motor activity of rats was measured following administration of cocaine alone and in combination with the centrally acting α 1-antagonist prazosin. Cocaine alone (18–42 mg/kg) increased motor activity in a dose-related manner. At doses of 1 and 1.8 mg/kg, prazosin attenuated the increases in motor activity produced by cocaine. In rats responding under a fixed-ratio discrimination procedure, (10–32 mg/kg) produced dose-dependent increases in percent errors and decreases in overall response rate. Across a range of doses (0.32–3.2 mg/kg), prazosin failed to antagonize the effects of cocaine on responding under the discrimination procedure. Rather, the combined effects were frequently greater than those obtained with cocaine alone. The data suggest that in rats activation of α 1-adrenergic systems may mediate the effects of cocaine on motor activity but not on schedule-controlled behavior.

Changes of Spontaneous Motor Activity of Rats After Acute Exposure to Tributyltin Chloride

The effects of a single acute exposure to tributyltin chloride (TBTCl) on spontaneous motor activity (SMA) in home cage were studied in male Wistar rats. The rats were given TBTCl intraperitoneally at a dosage of 0, 1.6 or 3.3 mg/kg, and the SMA was measured for five days after administration of TBTCl. Body weight gain in the 3.3 mg/kg group was significantly lowered, but that in the 1.6 mg/kg group was comparable to that in the control group. The SMA during light phase was not affected by TBTCl treatment. However, the SMA during dark phase was decreased in both of the TBTCl-treated groups. These decreases in SMA gradually returned to the control levels. The 24-hr total daily and 12-hr nocturnal activity in the TBTCl-treated groups were decreased in a dose-dependent manner. These data indicate that TBTCl possesses behavioral toxicity and suggest that the decreased nocturnal SMA is a sensitive index for detecting toxicity of chemicals in rats.

Interaction of high pressure and a narcotic dose of ethanol on spontaneous behavior in rats

This study analyses the spontaneous motor activity of rats that had received a narcotic dose of ethanol (3.5 g/kg) and were then exposed to 1 atmosphere absolute pressure (ATA) air or to 1 or 72 ATA of helium-oxygen (heliox). The ambient temperature was adjusted to offset ethanol- and helium-induced hypothermia. Ethanol administration prevented the occurrence of convulsions but did not alter the total number of myoclonic jerks at stable pressure. The ethanol-intoxicated animals exposed to high pressure did not exhibit normal locomotion but showed a trend towards increased activity during the last observation period. Similar blood and brain concentrations of ethanol were found in the 1 and 72 ATA groups. These results show that exposure to 72 ATA for 40 min started to exert some antagonistic effects, and they suggest that exposure to higher pressures or for a longer period of time may be sufficient to significantly offset the depressant effects of a narcotic dose of ethanol on spontaneous behavior in rats. At the same time, ethanol seems to protect against some aversive effects of high pressure.

Central dopaminergic actions of YM-14673, a new TRH analogue, in rodents

The effects of a new TRH analogue, YM-14673 (N α-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate) on spontaneous movement, sniffing, climbing, licking, biting and circling behaviors were compared with those of TRH and methamphetamine, in rodents. YM-14673 in a dose of 1 mg/kg (i.p.) enhanced spontaneous motor activity in rats, and induced sniffing and climbing behaviors in mice. The licking and biting behaviors were not induced by administration of YM-14673 even in a high dose (30–100 mg/kg i.p.) to mice. In addition, ipsilateral circling did not follow the i.p. administration of YM-14673 in rats receiving cis-flupenthixol unilaterally into the striatum. YM-14673 was about 20–30 times more potent than TRH to induce sniffing and climbing behaviors and to increase spontaneous movement. The sniffing and climbing behaviors induced by administration of YM-14673 and TRH were antagonized by treatment with haloperidol and α-methyl-para-tyrosine ( α-MT). Methamphetamine (0.5–10 mg/kg i.p.), unlike YM-14673, showed significant pharmacological effects in all behavioral experiments, so that the pharmacological profile of YM-14673 was different from that of methamphetamine. These results suggest that both YM-14673 and TRH induced behavioral changes, presumably due to facilitatory effects on the central dopaminergic system.

Time-dependent effects of intrahypothalamic injection of vasoactive intestinal peptide on spontaneous motor activity in rats.

In male Wistar rats, microinjection cannulae were stereotaxically implanted in the ventromedial and paraventricular hypothalamic nuclei. After control recordings of spontaneous motor activity for 4-6 days, vasoactive intestinal peptide (VIP) was injected in a dose of 1.0 microgram and a volume of 2.0 microliters into these nuclei at 1100 or 1900 h, and the activity during the 3-h period following was compared with that on the control days in individual animals. VIP injection produced an increase when injected at 1100 h, and a decrease when injected at 1900 h. Thus, a time-dependent fluctuation in the VIP effect on the hypothalamic neuronal activity was suggested.

Differential effects of the new antipsychotic risperidone on large and small motor movements in rats: a comparison with haloperidol

Risperidone, a new antipsychotic agent, was studied for its effects on spontaneous motor activity in rats in comparison with haloperidol. Motor activity was recorded via the optical scanning technique (horizontal and vertical activity) and via a recently developed technique based on the piezo-electric principle which, in contrast to optical scanning, is very sensitive to small, stationary movements (piezo activity). Risperidone and haloperidol at low doses depressed both vertical activity (ED50s: 0.062 and 0.038 mg/kg, respectively) and horizontal activity (0.18 and 0.060 mg/kg, respectively). With increase of dose, motor activity decline was significantly faster with haloperidol than with risperidone. Moreover, haloperidol also rapidly depressed piezo activity (ED50: 0.085 mg/kg) whereas risperidone depressed this component of motor behaviour at much higher doses only (ED50: 2.80 mg/kg). Visual inspection did not reveal abnormal behavioural movements following the test compounds. Risperidone, therefore, preserves normal small movements over a much larger dose interval than haloperidol; this effect may be related to its relatively low cataleptogenic activity and potentially also to a reduced EPS liability. The present results further confirm that the piezo technique may complement the optical scanning method, and thereby enhance the information on the extent that test compounds modify behaviour.

Measurement of spontaneous motor activity by using the vibrator response method in rats

To investigate the usefulness of spontaneous motor activity (SMA) measurement using the vibrator response method, the acute effects of drugs on SMA were observed in Sprague-Dawley male rats. There were no significant differences between four devices. Methamphetamine (0.3-1 mg/kg, i.p.) and 1-2 mg/kg (s.c.) of apomorphine increased the SMA, but 0.05-0.2 mg/kg (s.c.) of apomorphine decreased the SMA. Apomorphine at 1-2 mg/kg (s.c.) significantly increased the SMA when the vibrator response method was used as compared with the Animex method. These results suggest that the vibrator response apparatus is useful for the measurement of SMA in rats.

Serotonergic involvement in pharmacological action of the anxiolytic- sedatives thalidomide and supidimide

The anxiolytic-sedative drugs thalidomide and supidimide inhibited spontaneous motor activity in rats. Both compounds inhibited the serotonin (5-HT) behavioural syndrome induced by tranylcypromine (TCP) plus L-tryptophan (TRP) or clorgyline plus the selective 5-HT uptake blocker, LM 5008 (4-[2-(3-indolyl)ethyl]piperidine) and delayed the behavioural effects of p-chloro-amphetamine, a releaser of 5-HT. The behavioural syndrome induced by the 5-HT agonist, 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT) was unaffected by supidimide pretreatment. Thus supidimide does not possess 5-HT receptor antagonistic properties. This was further substantiated by the unaltered 5-HT-induced platelet aggregation in the presence of supidimide (10(-7)-10(-4) M). A decrease of 5-HT release into the synaptic cleft will lead to a diminished behavioural response to drugs that act presynaptically. Supidimide induced a greater increase in accumulation of brain 5-HT in TCP (5 mg/kg) plus TRP (100 mg/kg)-treated animals as compared to that in the corresponding controls. These data indicate that the behavioural and pharmacological actions of supidimide may be related to its inhibition of 5-HT release.

The development of tolerance to the depressant effect of arginine-8 vasopressin on the spontaneous motor activity of rats

Arginine-8 vasopressin (1.0 IU kg , s.c.) reduced the spontaneous motor activity of rats with no previous experience of the drug. Daily administration of arginine vasopressin (1.0 IU kg , s.c., once daily) to rats resulted in the gradual development of tolerance to the depressant effect of the drug on spontaneous activity. In further experiments, rats with no previous experience of the activity box, but chronically treated with arginine vasopressin (1.0 IU kg , s.c, 3 times daily), also displayed tolerance to the depressant effect of the drug. The development of tolerance was therefore dependent on repeated exposure to vasopressin and not on repeated experience of the activity box.

Short-term variations in diet composition change the pattern of spontaneous motor activity in rats.

The nocturnal activity patterns of rats changed significantly within 3 days after they were given unrestricted access to isocaloric diets in which the ratio of carbohydrate to protein was systematically varied. As the ratio increased, the rats were more continuously active. The subjects showed similar responses to variations in this ratio whether the diet contained 15 or 45 percent fat. No correlation was found between the number of calories an animal ate and its activity pattern.

Behavioral and neurochemical effects of repeated administration of Δ 9-tetrahydrocannabinol in rats

The effects of repeated administrations of Δ 9-tetrahydrocannabinol (THC, 10 mg/kg i.p. twice daily at 8-hr interval) were investigated on spontaneous motor activity (SMA) in 2.5 hr daily sessions and on the levels of various neurotransmitters (e.g. norepinephrine, NE; dopamine, DA; serotonin, 5-HT) in different brain areas such as caudate nucleus (CN), pons-medulla (PM) and diencephalon-midbrain (DM) in rats. After a single dose of the drug, the SMA of rats decreased during the first hour postdrug along with a decrease of DA levels in the CN and DM and NE levels in the DM and PM, and increase of 5-HT levels in the DM and PM. Following repeated daily administration, the SMA gradually decreased during the first hour postdrug to a minimum on day 5, and then increased beyond the normal level on day 8 reaching its peak on day 10. The SMA then decreased again and remained close to the normal level on day 15 onwards. Concomitantly, DA and NE levels decreased to their minimum, and 5-HT levels increased to their maximum in the respective brain areas on day 5; the levels of neurotransmitters then gradually approached their normal up to day 15. Thus, during the first hour after repeated administration of THC, the changes in behavioral depression can be correlated to the changes in the brain neurotransmitter levels. During the second hour of THC action, SMA was enhanced. On its repeated administration, this increase was gradually reduced up to day 6 after which SMA was again increased to its peak between day 8 and day 10 and then decreased. These behavioral changes could also be correlated with the changes in DA and 5-HT levels in the brain areas during the second hour postdrug after repeated administration.

The effect of probenecid on spontaneous motor activity in rats

Probenecid (200 mg/kg) administered intraperitoneally (i.p.), a dose routinely used in the measurement of cerebral monoamine turnover, produces marked decreases in the spontaneous motor activity in rats. The onset of the response is observed in less than 5 minutes and persists for 130–140 minutes. The sedation is apparently dose-related. These results suggest that probenecid may influence other central processes in addition to the acid transport system of the choroid plexus; therefore, the validity of probenecid as a tool for estimation of cerebral amine turnover is questioned.

Neuroanatomical focus for morphine and enkaphalin-induced hypermotility

OPIATE receptors, through which all opiate alkaloids and peptides produce their pharmacological effects, are distributed heterogeneously in the mammalian brain1–3. The highest receptor densities seem to be associated with a number of limbic midbrain and forebrain structures that have been implicated in regulating motivation and emotionality. Although the limbic midbrain region (periven-tricular-periaqueductal grey matter) is a critical focus for the analgesic4–7 and depressant (A.P. and C.S., in preparation) effects of morphine and enkephalin8, nothing is known about the functional significance of opiate receptors in the forebrain. Significantly, the nucleus accumbens (NA) in the limbic forebrain contains a relatively high concentration of opiate receptors2 (C. B. Pert, personal communication). As this structure has a role in motility9,10, an attempt has been made to ascertain whether it is an important focus for the excitatory effects11,12 of opiates on behaviour. We report here that direct injections of morphine. D-Ala4-enkephalin-amide (an enzyme-resistant enkephalin)7,12 and apomorphine (a dopamine agonist) into the nucleus accumbens increased spontaneous motor activity in rats. The excitatory effects of morphine were antagonised by naloxone (an opiate antagonist) and not by haloperidol (a dopaminergic antagonist). Conversely, apomorphine was antagonised by haloperidol and not by naloxone.

The tryptolines: Effect of intraventricular administration on spontaneous motor activity of rats

The pharmacologic properties of the tryptolines, hindered analogues of the tryptamines, were studied behaviorally in rats. Following intraventricular injections, it was found that spontaneous motor activity decreased markedly during the initial 25 mins when compared with saline. Since both the tryptolines and tryptamines have been shown to be inhibitors of 5-hydroxytryptamine uptake, it may be possible that these compounds are acting indirectly through an effect on the serotonergic system.

Combinations of selected CNS depressants with d-amphetamine or mazindol on food intake and motor activity of rats

Amobarbital, diazepam, prochlorperazine and thioridazine were tested alone and in combination with d-amphetamine or mazindol on food consumption and spontaneous motor activity in rats. Of the four depressants tested (1) only amobarbital enhanced the anorexic effects of d-amphetamine and (2) amobarbital, diazepam and prochlorperazine enhanced the hypermotility induced by d-amphetamine. None of the depressants altered the anorexic effect of mazindol but amobarbital and diazepam decreased and prochlorperazine increased the hypermotility induced by mazindol. These differential effects of the CNS depressants suggest that d-amphetamine and mazindol might have different mechanisms of anorexiant or stimulatory action. The data also suggest that, to achieve anorexia with diminished CNS stimulation, combinations of d-amphetamine and any of the tested CNS depressants seem to be precluded. In fact, this desired clinical objective might be achieved with combinations of mazindol and either amobarbital or diazepam.

The inhibitory effect of intraventricular administration of serotonin on spontaneous motor activity of rats

Spontaneous motor activity was studied following injection of 1, 10 and 50 mug of serotonin (5-HT) into the lateral ventricle of chronically cannulated rats. During the first 15 min, the rats receiving the higher doses of 5-HT showed significant decrements (P less than 0.01) in motor activity compared to saline controls. No activation was observed in either group. After 20 min, no significant differences for any treatment condition compared to saline controls were observed. It is concluded that a principal effect of directly increasing brain 5-HT concentration is to decrease activity. Possible mechanisms for this effect are discussed.

Blocking of the effect of Δ 1tetrahydrocannabinol (ΔTHC) on spontaneous motor activity in the rat by immunization with a protein conjugate of Δ 1THC

Rats actively immunized with porcine gamma globulin- hemisuccinate- Δ 1-tetrahydrocannabinol (PγG-HS-Δ 1THC) showed higher spontaneous motor activity after intraperitoneal administration of Δ 1THC at a dose of 10 mg. per kg. than did rats immunized with a control antigen, porcine gamma globulin-hemisuccinate-phenol (PγG-HS-Phenol). The capacity to neutralize the effect of Δ 1THC was found to depend on the degree of immunization; thus, the difference in mean spontaneous motor activity after injection of Δ 1THC was significant in rats which had received five injections of the immunogen over a period of 86 days, and not in those which had received only two injections over a period of 34 days. In view of the observations that Δ 1-tetrahydrocannabinol induces a decrease in spontaneous motor activity in rats, the observed neutralization of the effect of δ 1THC in animals receiving multiple injections of protein conjugates of Δ 1THC may be due to the binding of the drug by anti-THC antibodies (which are expected to be produced on active immunization with these conjugates), thus preventing Δ 1THC from reaching drug-receptor sites.

Correlation between brain adenyl cyclase activity and spontaneous motor activity in rats after chronic reserpine treatment

Reserpine (0.5 mg/kg) was administered daily to rats for a period of 8–12 days. Motor activity was measured 23–24 h after each injection. Twenty-four hours subsequent to the last reserpine injection, animals were sacrificed for determination of whole brain catecholamine concentration and adenyl cyclase activity. Rats which had shown a depression of motor activity after 3 days of treatment were hyperactive after 8–12 days. Brain norepinephrine concentrations in reserpine-treated animals ranged from 5 to 11% of control levels. In brain preparations from reserpine-treated rats, basal adenyl cyclase activity was unchanged from control, but the stimulation of cyclase activity produced by 10−4M norepinephrine was more than twice as great as that seen in controls. There was a strong positive correlation between the change in motor activity and the response of adenyl cyclase to norepinephrine, suggesting that the change in adenyl cyclase responsiveness may account for some of the increase in spontaneous activity occurring in rats after chronic reserpine treatment.

Development of spontaneous motor activity in rats in the embryonic and early postnatal periods

Development of spontaneous motor activity in rats in the embryonic and early postnatal periods

Magnesium pemoline: Enhancement of spontaneous motor activity

Magnesium pemoline, a mild central nervous system stimulant, increased spontaneous motor activity in rats within 35 min after injection. The effects persisted throughout the 30 min period of observation. Three days later, during the post-drug phase, the drug group exhibited less activity than the control group. If valid, this “rebound” phenomenon may be explained by a central homeostatic inhibitory mechanism which limits overt activity after a period of prolonged hyperexcitability.