The modulatory role of M2 muscarinic receptor on apomorphine-induced yawning and genital grooming

The interaction between dopaminergic and cholinergic pathways in the induction of behavioral responses has been previously established. In the brain, M2 receptors are found predominantly in presynaptic cholinergic neurons as autoreceptors, and in dopaminergic neurons as heteroceptors, suggesting a control role of acetylcholine and dopamine release, respectively. Our aim was to investigate the role of M2 receptors on the yawning and genital grooming of rats induced by apomorphine, a dopaminergic receptor agonist, focusing on the interaction between cholinergic and dopaminergic pathways. Initially, the effect of atropine, a non-selective muscarinic antagonist, on yawning and genital grooming induced by apomorphine (100 μg/kg s.c.) was analyzed. Atropine doses of 0.5, 1 and 2 mg/kg i.p. were administered to Wistar rats 30 min before induction of the behavioral responses by apomorphine. Number of yawns and time spent genital grooming were quantified over a 60 min period. Apomorphine-induced yawning was increased by low dose (0.5 mg/kg i.p.) but not by high doses (1 and 2 mg/kg, i.p.) of atropine. Genital grooming was antagonized by 2 mg/kg i.p. of atropine and showed no changes at the other doses tested. Tripitramine, a selective M2 cholinergic antagonist, was used as a tool for distinguishing between M2 and all other muscarinic receptor subtypes in yawning and genital grooming. Tripitramine doses of 0.01, 0.02 and 0.04 μmol/kg i.p. were administered to Wistar rats 30 min before apomorphine (100 μg/kg s.c.). Number of yawns and time spent genital grooming were also quantified over a 60 min period. Tripitramine 0.01 μmol/kg increased all parameters. Higher doses, which possibly block all subtypes of muscarinic receptor, did not modify the response of apomorphine, suggesting a non-selective effect of tripitramine at these doses. Given that low doses of tripitramine increased the behavioral responses induced by apomorphine and that the main distribution of the M2 receptor is presynaptic, we raised the hypothesis that tripitramine may alter cholinergic and/or dopaminergic transmission in brain areas responsible for induction of yawning and genital grooming in rats, possibly by control of acetylcholine and/or dopamine release. In addition, the present study showed the involvement of M2 cholinergic receptors in the complex mechanisms of functional interactions between dopaminergic and cholinergic systems involved in the control of yawning and genital grooming.     

Effects of apomorphine on rat behavior in the elevated plus-maze

It has been reported that novelty may evoke both an exploratory and a fear drive, thus generating behavior responding to an approach/avoidance conflict. However, not much is known about the approach component. Whereas there exists abundant evidence referring to the avoidance component as the main target for the anxiolytic action of benzodiazepines, the involvement of dopaminergic mechanisms in fear and anxiety is controversial. The present study examined the effects of the dopaminergic agonist apomorphine, the D₂ dopaminergic antagonist sulpiride and the combined treatment sulpiride plus apomorphine on conventional and non-conventional measures of the behavior of rats exposed to an elevated plus-maze. Systemic injection of apomorphine (0.25, 0.5 and 1.0 mg/kg) caused a selective increase in the time spent in the open arms and in the open arm extremities. Pre-treatment with sulpiride blocked these effects while this dopaminergic antagonist had no effect by its own. Apomorphine produced no significant effects on stretching, flat-back-approach or scanning. Therefore, apomorphine increased the behavioral response linked to the approach component of the conflict without affecting risk assessment behaviors. These findings suggest that dopaminergic mechanisms, probably through D₂ receptors, may also be involved in the mediation of the conflict derived from the need of gathering information for confirming, identifying and localizing danger and take the appropriate action for avoiding the threatening stimuli of the elevated plus-maze. A role for dopaminergic mechanisms in the setting up of adaptive responses in a fear-inducing environment is discussed.     

The synaptic excitation of Renshaw cells

Summary An analysis has been made in spinal cats anaesthetised with pentobarbitone of the firing of Renshaw cells induced by stimulation of ventral roots or by volleys entering the spinal cord via dorsal root fibres. The response to maximal ventral root stimulation consisted of an early high frequency discharge which was blocked by dihydro--erythroidine (nicotinic receptors), a depression of spontaneous firing and a subsequent late firing which was specifically depressed by atropine (muscarinic receptors). The intervening depression or pause was associated with a non-specific depression of the sensitivity of these neurones to both acetylcholine and excitant amino acids. It is proposed that these responses may be the consequence of the action of acetylcholine released simultaneously from all of the axon collateral endings upon a Renshaw cell and that the late response may have no functional role. Other possibilities are discussed. The spontaneous activity of these neurones appears to involve muscarinic receptors. The activation of Renshaw cells by dorsal root volleys, which is independent of the prior discharge of motoneurones, does not involve cholinergic mechanisms.     

Influence of dopamine-like compounds on stereotypy and locomotor activity in atropinized rats.

The influence of atropine on stimulation of exploratory activity, locomotor activity and stereotypy in rats treated with compounds which stimulate central dopamine receptors (apomorphine, D-amphetamine, D-145 and piribedil) was studied. Atropine potentiated the action of these compounds in some experimental systems. The results are discussed from the point of view of an equilibrium between the dopaminergic and cholinergic systems in the central nervous system.     

Release of gastrin on stimulation of the sciatic and brachial nerves of the cat

The vasomotor response of dopamine and dopaminergic agonists was studied in vitro on middle cerebral arteries from cat and pial arteries from humans. The action of various inhibitors was tested in order to define the receptors involved. A contractile response could be obtained by epinine, apomorphine and dopamine in the mentioned order of potency. The effect was blocked by alpha-receptor as well as serotonin receptor antagonists. The mode of inhibition suggested that serotonin receptors rather than alpha-adrenoceptors mediated the dopamine-induced contraction. A dose-dependent dilatation could be evoked by the dopaminergic agonists on actively contracted pial arteries. The relative potency was epinine > dopamine > apomorphine. The order of potency for the agonists, together with blocking experiments (including a parallel shift in the log dose-response curve induced by bulbocapnine), indicated that the vasodilatation is mediated by specific dopamine receptors.     

Effects of vagotomy and glossopharyngectomy on respiratory response to dopamine-agonists

In normal rats lightly anesthetized with halothane apomorphine increased both resting and CO₂-_-dependent minute ventilation (V_M) by stimulating respiratory frequency (RF) whereas tidal volume (V_T) was slighly decreased. Acute bilateral glossopharyngectomy, which impaired carotid body function, did not change the apomorphine effects in contrast to bilateral vagotomy, which abolished the RF response of the drug, but now increased V_T. Intravenous infusion of dopamine increased V_M, by elevating RF, and this effect was only slightly blunted by bilateral glossopharyngectomy but nearly abolished by vagotomy and totally eliminated by the combined procedures. The respiratory response to dopamine was depressed in rats with chronically destroyed central catecholaminergic neurons. These findings indicate that there may be two different dopaminergic stimulatory mechanisms that modulate RF—one peripheral and one central—and both depend upon afferent vagal activity. With impaired vagal function, however, two other dopaminergic stimulatory mechanisms effecting V., are evident—one central, and one peripheral which involves the carotid body.     

Adrenergic and cholinergic mechanisms of hemopoiesis regulation during experimental neuroses

Scopolamine abolished hyperplasia of erythropoiesis caused by conflict situation and its inhibition after paradoxical sleep deprivation, but did not affect granulomonocytopoiesis. The modulatory effects of this muscarinic receptor blocker on the erythron indicated involvement of the cholinergic system in the formation of neurotransmitter interrelations.In vitro restoration of the colony-forming ability of myelokaryocytes under the effect of sympathomimetics duringin vivo blockade of the central or peripheral part of the adrenergic system indicated that adrenoceptors play the major role in the information transfer from the higher regulatory centers to hemopoietic cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 4, pp. 381–385, April, 2000     

Increased burst firing in substantia nigra pars reticulata neurons and enhanced response to selective D2 agonist in hemiparkinsonian rats after repeated administration of apomorphine

Intermittent administrations of dopaminergic agents in hemiparkinsonian rat enhances the behavioral response to subsequent administration of the drugs. This phenomenon is known as "priming" and thought as comparable to drug-induced dyskinesia in patients with Parkinson's disease. We investigated the behavioral and electrophysiological changes in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats after repeated administrations of apomorphine. Administration of apomorphine (0.32 mg/kg, intraperitoneal, i.p.) twice daily for 6 days enhanced the rotation induced by apomorphine from 341 turns/hour at the beginning to 755 turns/hr at the end. At the same time, the response to selective D2 agonist quinpirole (0.26 mg/kg, i.p.) was also enhanced from 203 to 555 turns/hr. Extracellular single unit recording revealed no significant difference in the basal firing rates of substantia nigra pars reticulata (SNr) neurons between the ipsilateral and contralateral side of the 6-OHDA lesion regardless of the repeated administrations of apomorphine. In SNr of the lesion side, the units with burst firing pattern were found more frequently after repeated administrations of apomorphine and the suppressive effect of quinpirole on the firing rate was enhanced. These findings suggest that the increased percentage of the burst units is the important electrophysiological change in the development of enhanced response to selective D2 agonist.     

Expression of neuropeptide Y immunoreactivity in the rat nucleus accumbens is under the influence of the dopaminergic mesencephalic pathway

Summary The density of neuropeptide Y (NPY) immunostained neurons examined in the rat nucleus accumbens (NAcc) was shown to be constant across the anteroposterior extent of the nucleus and did not present any right-left hemispheric difference. Selective unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigral dopaminergic neurons induced, 15 to 21 days later, a bilateral decrease in the NPY neuron density which was, interestingly, more marked in the contralateral than in the ipsilateral NAcc. Dopamine depletion induced by -methylparatyrosine treatment elicited a decrease in NPY neuronal density similar in amplitude to that induced by the 6-OHDA lesion in the ipsilateral NAcc suggesting that similar mechanisms underly both NPY responses. In both experimental conditions, changes in NPY immunostaining were quite homogeneous in the two antero-posterior NAcc portions arbitrarily considered. Apomorphine treatment in animals with 6-OHDA injury completely reversed the ipsilateral lesion effect in the anterior part of the NAcc but only partially the contralateral one. In contrast, no significant effect of apomorphine was observed in either side of the NAcc posterior portion. This data suggests the involvement of at least 2 components in the NPY neuron responses to the lesion. The component reversed by apomorphine treatment was presumed to be directly linked to the DA depletion, while the second component not antagonized by apomorphine was considered independant on DA transmission. These data therefore provide morphological evidence for the occurence of complex functional interactions between dopaminergic afferents and NPY-containing neurons within the NAcc.Laboratoire associé à l'Université Aix-Marseille II, Faculté des Sciences de Luminy     

Imprinted DC mediate the immune‐educating effect of early‐life microbial exposure

It has been long proposed that exposure to environmental factors early in life may have an educating effect on the development of immune regulatory functions. However, experimental studies on this issue are limited and the related molecular and cellular basis remains unclear. Here we report that neonatal exposure to killed bacteria (Chlamydia muridarum, originally called Chlamydia trachomatis mouse pneumonitis (MoPn)) changed the pattern of the hosts' immune responses to a model allergen (OVA) in adulthood. This was associated with altered phenotype and function of DC. We found that DC from adult mice treated neonatally with UV‐killed MoPn exhibited distinct patterns of surface marker and TLR expression and cytokine production from control mice (DC from adult mice neonatally treated with vehicle, (Sham‐DC)). More importantly, DC from adult mice treated neonatally with UV‐killed MoPn induced significantly lower type‐2 antigen‐specific T‐cell responses than Sham‐DC shown in DC:T co‐culture experiments in vitro and in adoptive transfer experiments in vivo. In addition, depletion of T cells in vivo largely abolished the phenotypic and functional alterations of DC caused by bacterial exposure, suggesting the involvement of T cell in this process. Our study demonstrates a central role of DC in linking the early‐life exposure to microbial products and the balanced development of immune regulatory functions and the involvement of T cells in imprinting of the DC function.     

Role of dopaminergic system in opioid-induced cardiovascular responses in dogs

A study was carried out to determine the involvement of dopaminergic system in opioid-induced cardiovascular responses in the dogs. The study population consisted of 32 mongrel dogs of either sexes. The results show that morphine given in small dose (2 mg/kg I.V.) causes significant fall in blood pressure. The results also show that there is involvement of dopaminergic system in opioid-induced vasomotor responses in dogs. Partial blockade of the parenterally induced hypotensive response of morphine by haloperidol given centrally induced hypotensive responses of morphine by haloperidol given centrally in doses, which are too low to be effective by the peripheral route, strongly favours the involvement of central dopaminergic system in the morphine-induced hypotensive responses. The results also show that the hypotensive response of morphine was almost completely blocked after naloxone pretreatment by central route.     

Possible Mechanisms of the Involvement of Dopaminergic Cells and Cholinergic Interneurons in the Striatum in the Conditioned-Reflex Selection of Motor Activity

A possible mechanism for the involvement of cholinergic interneurons in the striatum and dopaminergic cells in the substantia nigra in the selection from among several types of motor activity during learning is proposed. Selection is triggered by simultaneous increases in the activity of dopaminergic neurons and a pause in the activity of cholinergic interneurons in response to the conditioned signal. The appearance of the pause may facilitate activation of GABAergic interneurons in the striatum and the action of dopamine on D2 receptors on cholinergic interneurons. Differently directed changes in dopamine and acetylcholine levels synergistically modulate the efficiency of corticostriatal inputs, such that the rules for modulation of the “strong” and “weak” inputs are opposite in sign. The subsequent reorganization of neuron activity in the cortex-basal ganglia-thalamus-cortex circuit leads to increased activity in those cortical neurons providing “strong” innervation to the striatum with simultaneous decreases in the activity of neurons providing “weak” innervation to the striatum, which may underlie the selection of the movement reaction, in which the neocortex is involved. It follows from this model that if the delay between the conditioned and unconditioned stimuli is not longer than the latent period of the reactions of dopaminergic and cholinergic cells (about 100 msec), selection of movement activity in response to the conditioned signal and learning is hindered. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 54, No. 6, pp. 734–749, November–December, 2004.     

Serotonergic mechanisms are necessary for central respiratory chemoresponsiveness in situ

Evidence from in vivo and in vitro experiments conclude that serotonin (5-HT) neurons are involved in and play an important role in central respiratory CO₂/H⁺ chemosensitivity. This study was designed to assess the importance of 5-HT neurons and 5-HT receptor activation in the frequency and amplitude components of the hypercapnic response of the respiratory network in the unanesthetized perfused in situ juvenile rat brainstem preparation that exhibits patterns of phrenic nerve discharge similar to breathing in vivo. Exposure to a hypercapnic perfusate increased phrenic burst frequency and/or amplitude, the neural correlates of breathing frequency and tidal volume in vivo. Hypercapnic responses were also assessed during exposure to ketanserin (5-HT₂ receptor antagonist), and 8-OH-DPAT (inhibiting 5-HT neurons via 5-HT_1A autoreceptors). Neither of these drugs substantially altered baseline activity, however, both abolished hypercapnic responses of the respiratory network. These data illustrate that 5-HT neurons and 5-HT receptor activation are not required for respiratory rhythm generation per se, but are critical for CO₂ responses in situ, supporting the hypothesis that 5-HT neurons play an important role in central ventilatory chemosensitivity in vivo.     

Acetylcholinesterase activity in the brain of dystonia musculorum (Dst(dt-J)) mutant mice

The dystonia musculorum (Dst^dt-J) mutant mouse suffers from severe motor coordination deficits, characterized, among various symptoms, by a spastic ataxia and dystonic movements, indicating central defects in motor structures in addition to dystrophy of peripheral sensory tracts and partial degeneration of spinocerebellar tracts. Neurochemical alterations, notably in dopaminergic and noradrenergic systems, were previously observed in basal ganglia and cerebellum. A quantitative histochemical cartography of brain acetylcholinesterase activity in Dst^dt-J mutants, in comparison with controls, revealed increases in the neostriatum, the habenula-interpeduncular pathway, the cholinergic pedunculopontine nucleus and its target structures, the thalamus, major regions of the basal ganglia, such as substantia nigra, ventral tegmental area, globus pallidum, and subthalamic nucleus, as well as in associated extrapyramidal regions, such as red nucleus, brainstem reticular formation, and superior colliculus. These acetylcholinesterase changes may play a role in motor deficits, particularly the dystonic symptomatology observed in the mutation.     

Induction of the monooxygenase system in rat blood neutrophils by methylcholanthrene and sovolin vivo and its effects on the properties of these cells

The xenobiotics methylcholanthrene and sovol (the latter being a mixture of polychlorinated biphenyls), which are monooxygenase system inducers, were tested for their effect on the respiratory burst in rat blood neutrophilsin vivo. The chemiluminescence accompanying this burst was more intensive in the neutrophils of rats treated with methylcholanthrene or sovol than in untreated rats. Observed changes in the 2A_max parameter of the electron paramagnetic resonance spectrum recorded for the spin probe 5-doxyl stearate in the presence of neutrophils indicated that methylcholanthrene and sovol can exert a direct effect on the viscous properties of neutrophil plasma membranesin vivo. These changes were similar in direction to those in the intensity of chemiluminescence during the respiratory burst in neutrophils. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 11, pp. 485–488, November, 1995 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

Activation of calcium/calmodulin-dependent protein kinase IIα in the striatum by the heteromeric D1-D2 dopamine receptor complex

Synaptic plasticity in the striatum is a key mechanism that underlies processes such as reward related incentive learning and behavioral habit formation resulting from drugs of abuse. Key aspects of these functions are dependent on dopamine transmission as well as activation of calcium/calmodulin-dependent protein kinase IIα (CaMKIIα). In this study, we examined the ability of a recently identified heteromeric complex composed of D1 and D2 dopamine receptors coupled to Gq/11 to activate striatal CaMKIIα. Using the dopaminergic agonist SKF83959, which selectively activates the D1-D2 complex, we demonstrated phosphorylation of CaMKIIα at threonine 286, both in heterologous cells and in the murine striatum in vivo. Phosphorylation of CaMKIIα by activation of the receptor complex required concurrent agonism of both D1 and D2 receptors and was independent of receptor pathways that modulated adenylyl cyclase. The identification of this novel mechanism by which dopamine may modulate synaptic plasticity has implications for our understanding of striatal-mediated reward and motor function, as well as neuronal disorders in which striatal dopaminergic neurotransmission is involved.     

Intrapallidal injection of 6-hydroxydopamine induced changes in dopamine innervation and neuronal activity of globus pallidus

The globus pallidus (GP) plays an important role in basal ganglia circuitry. In contrast to the well-characterized actions of dopamine on striatal neurons, the functional role of the dopamine innervation of GP is still not clearly determined. The present study aimed to investigate the effects of intrapallidal injection of 6-hydroxydopamine (6-OHDA) on rotational behavior induced by apomorphine, on the loss of dopamine cell bodies in the substantia nigra pars compacta (SNc) and fibers in the GP and striatum and on in vivo extracellularly-recorded GP neurons in the rat. Injection of 6-OHDA into GP induced severe loss of tyrosine hydroxylase–immunoreactive (TH-IR) fibers in GP (−85%) with a reduction in the number of TH-IR cell bodies in the SNc (−52%) and fibers in the striatum (−50%). S.c. injection of apomorphine in these rats induced a moderate number of turns (26±6 turns/5 min). Electrophysiological recordings show that 6-OHDA injection in GP induced a significant decrease of the firing rate of GP neurons (16.02±1.11 versus 24.14±1.58 spikes/sec in control animals and 22.83±1.28 in sham animals, one-way ANOVA, P<0.0001) without any change in the firing pattern (χ²=1.03, df=4, P=0.90). Our results support the premise of the existence of collaterals of SNc dopaminergic axons projecting to the striatum and GP and that dopamine plays a role in the modulation of the firing rate but not the firing pattern of GP neurons. Our data provide important insights into the functional role of the SNc–GP dopaminergic pathway suggesting that dopamine depletion in GP may participate in the development of motor disabilities.     

Cholinergic terminals in the ventral horn of adult rat and cat: Evidence that glutamate is a cotransmitter at putative interneuron synapses but not at central synapses of motoneurons

Until recently it was generally accepted that the only neurotransmitter to be released at central synapses of somatic motoneurons was acetylcholine. However, studies on young mice (P0-10) have provided pharmacological evidence indicating that glutamate may act as a cotransmitter with acetylcholine at synapses between motoneurons and Renshaw cells. We performed a series of anatomical experiments on axon collaterals obtained from intracellularly labeled motoneurons from an adult cat and labeled by retrograde transport in adult rats to determine if glutamate is co-localized with acetylcholine by these terminals. We could find no evidence for the presence of vesicular glutamate transporters in motoneuron axon terminals of either species. In addition, we were unable to establish any obvious relationship between motoneuron terminals and the R2 subunit of the AMPA receptor (GluR2). However we did observe a population of cholinergic terminals in lamina VII which did not originate from motoneurons but were immunoreactive for the vesicular glutamate transporter 2 and formed appositions to GluR2 subunits. These were smaller than motoneuron terminals and, unlike them, formed no relationship with Renshaw cells. The evidence suggests that glutamate does not act as a cotransmitter with acetylcholine at central synapses of motoneurons in the adult cat and rat. However, glutamate is present in a population of cholinergic terminals which probably originate from interneurons where its action is via an AMPA receptor.     

Evidence for the absence of impulse-regulating somatodendritic and synthesis-modulating nerve terminal autoreceptors on subpopulations of mesocortical dopamine neurons

Electrophysiological and biochemical techniques were used to study midbrain dopamine systems. In the electrophysiological studies, projection areas of individual dopaminergic cells were identified by antidromic activation. Dopamine cells which innervate the piriform cortex and those that innervate the caudate nucleus demonstrated their usual dose-dependent inhibitory response to both the intravenous administration of the direct-acting dopamine agonist apomorphine and the microiontophoretic application of dopamine. In contrast, the firing rate of dopamine neurons which project to the prefrontal cortex and of those terminating in the cingulate cortex was not altered by either the intravenous administration of low to moderate doses of apomorphine or microiontophoretically applied dopamine. The mean basal discharge rate and degree of burst firing was also different between these subgroups of midbrain dopaminergic neurons. Mesoprefrontal and mesocingulate dopamine neurons had mean firing rates of 9.3 and 5.9 spikes/s respectively, and showed intense burst activity. Mesopiriform and nigrostriatal dopamine cells had discharge rates of 4.3 and 3.1 spikes/s and displayed only moderate bursting. The dopaminergic nature of those mesocortical neurons insensitive to apomorphine and dopamine was confirmed using combined intracellular recording and catecholamine histofluorescence techniques. Thus, after the intracellular injection of colchicine and subsequent processing for glyoxylic acid-induced histofluorescence, the injected cells could be identified by their brighter fluorescences compared to the surrounding, normally fluorescing, non-injected dopamine neurons. Using biochemical techniques, subgroups of midbrain dopaminergic systems were again found to differ. The administration of gamma-butyrolactone increased dopamine levels in all areas sampled (prefrontal, cingulate and piriform cortices as well as the caudate nucleus). However, although this effect was readily reversed in both the piriform cortex and caudate nucleus by pretreatment with apomorphine, this treatment had no effect on the increased dopamine levels observed in the prefrontal and cingulate cortices. In addition, the decline in dopamine levels after synthesis inhibition with alpha-methyltyrosine was significantly faster in the prefrontal and cingulate cortices relative to the caudate nucleus. The piriform cortex showed an intermediate decline which was not significantly different from that observed in any of the other regions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ontogenetic Development of Dopaminergic Regulation of Grooming Behavior in Rats

The effect of the developing nucleus accumbens and ventrolateral striatum on grooming behavior in rat pups (1st month of life) and adult rats (2-12 months of life) was studied during activation of D1 and D2 dopamine receptors with apomorphine. Over the 1st week of life, apomorphine treatment was followed by hypersensitivity of D1 receptors in the nucleus accumbens. It was manifested in the early appearance of scratching and washing movements during ontogeny. The effect of activation was reduced after neonatal gangliosympathectomy. D2 receptors in the nucleus accumbens are identifi ed on day 22 of life. D2 receptors in the ventrolateral striatum become functionally active during this period. Under these conditions, apomorphine increased signifi cantly the duration of licking and biting movements. The number of D2 receptors in the ventrolateral striatum increases sharply during sexual maturity (2nd month of life). These changes are accompanied by an increase in the duration of oral stereotyped behavior. The duration of grooming movements was signifi cantly reduced by the end of stereotyped behavior. The effect of apomorphine was most pronounced in 9-month-old animals. We conclude that the immature ventrolateral striatum has a reciprocal stimulatory effect on licking and biting movements during ontogeny. By contrast, the mature striatum produces a subordinate reciprocal inhibitory infl uence on various types of grooming movements.