Changes In Spontaneous Motor Activity Research Articles

The effect of neurotransmitters on cataleptic behavior induced by PG D 2 in rats

The effects of several neurotransmitters on prostaglandin (PG) D 2-induced cataleptic behavior in rats were investigated by the high bar test. Intracerebroventricular administration of PG D 2 elicited cataleptic behavior in a dose-dependent manner without producing a marked change in spontaneous motor activity. The incidences of cataleptic behavior were 20% and 100% at doses of 2 nmol and 50 nmol of PG D 2, respectively. Intraperitoneal pretreatment with L-DOPA (100 mg/kg), apomorphine (1 mg/kg), amantadine (0.2 mg/kg), atropine (0.5 mg/kg) or p-chlorophenylalanine (300 mg/kg) significantly decreased the cataleptic behavior induced by 50 nmol of PG D 2. Conversely, simultaneous treatment with 5-hydroxy-L-tryptophan (30 mg/kg), 5-methoxy- N,N-dimethyltryptamine (5 mg/kg), imipramine (20 mg/kg) or clomipramine (10 mg/kg) markedly increased the cataleptic behavior induced by 2 nmol of PG D 2. Propranolol (10 mg/kg) and phenoxybenzamine (10 mg/kg) did not affect the induction of cataleptic behavior by either 2 nmol or 50 nmol of PG D 2. These results suggest that PG D 2 might be involved in inducing cataleptic behavior by modulating serotonergic, cholinergic and dopaminergic systems.

Interaction between thyrotropinreleasing hormone and the mesolimbic dopamine system

The involvement of the mesolimbic dopamine (DA) system in the excitatory behavioral effects of thyrotropin-releasing hormone (TRH) has been a controversial topic. In this study TRH was injected into the nucleus accumbens, lateral ventricles or ventral tegmental area and changes in spontaneous motor activity and metabolism of DA in the nucleus accumbens and striatum measured. Injection of TRH into all three areas of the brain produced an increase in photocell counts of locomotor activity and, in the nucleus accumbens, a significant decrease in photocell counts of rearing was measured. Injection of TRH into the nucleus accumbens caused a marked increase in metabolism of DA in both the nucleus accumbens and striatum. A smaller increase in metabolism of DA was also observed after injection of TRH into the lateral ventricles, but no significant change was found after intra-ventral tegmental administration of TRH. These data indicate that while TRH probably acts in the nucleus accumbens to enhance the metabolism of DA, and presumably release of DA, the excitatory behavioral effect of TRH is only partially mediated by this dopaminergic mechanism.

Anxiolytic action of CGS 9896 on mouse exploratory behavior

A new non-benzodiazepine compound proposed as a non-sedating anxiolytic was tested in the mouse exploratory model of anxiety. CGS 9896 significantly increased the number of light dark transitions at doses beginning at 7.5 mg/kg i.p. Analysis of general locomotor activity at these doses revealed no change in spontaneous motor activity in a photocell equipped activity monitor. Pretreatment with the benzodiazepine receptor antagonist, Ro15-1788, 10 mg/kg i.p., blocked the increase in light dark transitions produced by CGS 9896. These data support the interpretation that CGS 9896 acts as an anxiolytic through the benzodiazepine receptor, and appears to have no sedating properties within the anxiolytic dose range.

Relationship of changes in spontaneous motor activity to spontaneous circling in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra

Two unilateral injections of 6-hydroxydopamine into the substantia nigra and ventral tegmental area of adult rats pretreated with desmethylimipramine produced severe unilateral depletions of limbic and striatal dopamine. These animals sustained global deficits in spontaneous motor activity with no recovery evident from 1 to 14 weeks postoperative. The frequency of spontaneous circling increased during the 1 st few weeks postoperative and then remained stable during the last 2 months of observation. The changes in circling were independent of changes in global spontaneous motor behaviors. Biochemical determinations indicated an increased dopamine turnover in residual limbic and striatal dopamine neurons but with substantially changed dihydroxyphenylacetic acid:homovanillic acid ratios. The absence of functional recovery of both normal and asymmetric motoric behavior indicates that severe uncompensated deficits in motoric function produced by unilateral 6-hydroxydopamine lesions can provide a useful animal model for the study of dopaminergic contributions to movement disorders.

Acute tryptophan pretreatment protects against behavioral changes caused by cerebral ischemia

Male gerbils ( Meronies ungulata) were treated with various doses of tryptophan and the changes in spontaneous motor activity determined. Tryptophan decreased behavior at a dose of 200 mg/kg. Cerebral ischemia was produced by bilateral carotid occlusion for 5 min. This duration of ischemia produced a large increase in activity at both 6 h and 24 h postischemia. Tryptophan (200 mg/kg) prevented the ischemia-induced increases in locomotor activity. These data suggest that dietary amino acids may play a role in determining the effects of ischemia.

Infusion of adrenergic receptor agonists and antagonists into the locus coeruleus and ventricular system of the brain: Effects on swim-motivated and spontaneous motor activity

These studies examined how pharmacological stimulation and blockade of alpha receptors would affect active motor behavior in rats. In experiment I, alpha-2 receptor antagonists (piperoxane, yohimbine) and agonists [clonidine, norepinephrine (NE)] were infused into various locations in the ventricular system of the brain, including the locus coeruleus region, and motor activity was measured. Activity was measured principally in a swim test but spontaneous (ambulatory) activity was also recorded while drugs were being infused. When infused into the locus coeruleus region, small doses of the antagonists piperoxane and yohimbine depressed activity in the swim test while infusion of the agonists clonidine and NE had the opposite effect of stimulating activity. These effects were highly specific to the region of the locus coeruleus, since infusions of these drugs into other nearby locations in the ventricular system or use of larger doses had different, often opposite effects. This was especially true of clonidine and NE which profoundly depressed activity when infused posterior to the locus coeruleus, particularly over the dorsal vagal complex. Infusion of small doses of these drugs into the lateral ventricle had effects similar to infusion into the locus coeruleus region, though less pronounced. Changes in spontaneous motor activity were also observed, but this measure differentiated the groups less well than did the swim test. In experiment II, the predominantly postsynaptic receptor agonists isoproterenol (beta agonist) and phenylephrine (alpha-1 agonist) were infused into the ventricular system. Since infusions of piperoxane and yohimbine into the locus coeruleus that decreased activity in experiment I increase the release of NE by blocking alpha-2 inhibitory receptors on cell bodies and dendrites of the locus coeruleus, experiment II tested whether ventricular infusion of predominantly postsynaptic receptor agonists would also decrease activity in the swim test. Both isoproterenol and phenylephrine produced this effect, but did so selectively with respect to dose and location of infusion in the ventricular system. These findings are consistent with recent results relating to the mechanism that underlies stress-induced depression of active behavior.

Substance K and substance P in the ventral tegmental area

A comparison was made between substance P (SP) and substance K (SK) in the ventral tegmental area (VTA) (A10 dopamine cell group) of the rat. Approximately equal densities of SP and SK-immunoreactive neuronal fibers were observed. However, while previous reports demonstrate negligible density of autoradiographically defined SP receptors in the VTA, we observed a high density of SK receptors. SK or SP was microinjected into the VTA, and changes in spontaneous motor activity were measured using a photo-cell apparatus. SK was found to be at least 10 times more potent than SP in producing an increase in motor activity. These data suggest that while both SK and SP are present in the VTA, SK may have a more significant physiological role in modulating dopamine neurons in the ventromedial mesencephalon.

Differential aversive stimulus properties of beta-phenylethylamine and of d-amphetamine.

In a conditioned taste-aversion experiment with male Wistar rats (two-bottle test, single pairing), the effects of beta-phenylethylamine (PEA 12.5, 25.0, 50.0, 100.0 mg/kg IP) and of d-amphetamine (2.5 mg/kg IP) were compared with the effect of the saline vehicle. The amphetamine-treated group exhibited a marked aversion to saccharin on each of four retention trials. A decrease in saccharin intake after PEA was limited to the highest dose group (100 mg/kg) and the first retention trial for that group. Doses of up to 50 mg/kg of PEA were also ineffective with a single-bottle conditioned taste-aversion procedure involving multiple conditioning trials, although doses of 25 and 50 mg/kg of PEA induced marked changes in spontaneous motor activity. These data demonstrate that behaviourally active doses of PEA are ineffective in inducing a conditioned taste aversion to saccharin. This result extends previous reports that structurally similar compounds may have different potencies in this paradigm. It is proposed that further studies of structure-activity relationships may help to reveal the features of drug action that are necessary for the induction of a conditioned taste aversion.

Behavioural and biochemical effects of dopamine and noradrenaline depletion within the medial prefrontal cortex of the rat

The effects of 6-hydroxydopamine (6-OHDA) lesions of catecholamine terminals within the medial prefrontal cortex on spontaneous motor activity, dopamine (DA)-dependent stereotyped behaviour and subcortical dopamine turnover were investigated in the rat. Two types of lesions were examined, bilateral injection of 6-OHDA into the medial prefrontal cortex of untreated rats (6-OHDA alone), and bilateral injection of 6-OHDA into the medial prefrontal cortex of animals pretreated with the noradrenaline (NA) uptake blocking agent desmethylimipramine (6-OHDA/-DMI). Ten days after surgery the 6-OHDA lesions produced no significant change in spontaneous motor activity and had no overall effects on stereotyped behaviour induced by apomorphine or (+)-amphetamine. This lesion caused gross depletion of NA within the medial prefrontal cortex and curiously, elevated DA concentrations within this site. No changes in DA concentration were recorded within subcortical sites, although concentrations of DA metabolites within striatum and nucleus accumbens were reduced. In contrast, the 6-OHDA/DMI lesion of the medial prefrontal cortex significantly enhanced spontaneous motor activity and amphetamine-induced stereotyped behaviour. Apomorphine-induced stereotypy, on the other hand, was significantly reduced. Biochemically the lesion caused a large depletion of DA with relatively little loss of NA within the medial prefrontal cortex. In addition, from this and another study (ref. 33), increases in DA and its metabolite concentrations were measured in striatum and nucleus accumbens, together with an apparent increase in DA turnover within these subcortical sites. It is thus apparent that in the absence of a substantial portion of the DA innervation of the medial prefrontal cortex, with a largely intact NA innervation, there is an increase in motor activity and amphetamine-induced stereotypy which may be related to functional changes in DA activity within subcortical telencephalic structures. Such a finding might suggest that DA within the frontal cortex has a behaviourally inhibitory role in the rat, although further work is required to substantiate this.

277 - Neuropharmacological studies on drug dependence (IV) Changes in spontaneous motor activity, EEG and brain monoamines during the period of dependence development and of abrupt withdrawal in rats.

277 - Neuropharmacological studies on drug dependence (IV) Changes in spontaneous motor activity, EEG and brain monoamines during the period of dependence development and of abrupt withdrawal in rats.

Drugs modifying dopaminergic activity and behaviour, the EEG and epilepsy in Papio papio

Acute changes in spontaneous motor activity, the EEG and photically induced epileptic responses have been observed in baboons ( Papio papio) following the i.v. injection of drugs acting on dopaminergic transmission. Apomorphine hydrochloride, 0.5–1.0 mg/kg, produced a phase of acute excitement with accentuated vigilance and abnormal buccal motor activity lasting 30–40 min; during this phase myoclonic responses to intermittent photic stimulation were absent. After piribedil (ET 495, 1,2″-pyrimidyl-4-piperonylpiperazine), 2–10 mg/kg, acute excitement was not seen. Intermittent δ activity was prominent in the EEG for 1–3 hr, and was associated with a slight reduction in photically induced epileptic responses. Haloperidol 0.6–1.2 mg/kg, produced a long-lasting reduction in spontaneous motor activity with an increased incidence of spontaneous EEG spikes and waves and a great enhancement of paroxysmal EEG activity during photic stimulation. Pimozide, 0.5–2.5 mg/kg, normally produced mild sedation and some EEG slowing. 2 animals responded idiosyncratically to both haloperidol and pimozide, displaying intermittent dystonic episodes with bucco-facial dyskinesia. These findings suggest that activation of dopaminergic receptors can lead to a reduction in myoclonic responses to photic stimulation.