Caudate Anterior Putamen Research Articles

Regional differences in evoked dopamine efflux in brain slices of rat anterior and posterior caudate putamen

Fast cyclic voltammetry using carbon fibre microelectrodes in rat brain slices, was used to investigate regional differences in electrically-evoked dopamine (DA) efflux at 10 different sites in the anterior caudate putamen (aCPu) and 10 sites in the posterior caudate putamen (pCPu). For each site DA overflow was evoked by both single pulse (1P) stimulation and by trains of 25 pulses applied at a frequency of 50 Hz (25P/50 Hz). Peak DA efflux evoked by 1P was about 58% greater in the aCPu (0.19 mumol/l DA) than in the pCPu (0.12 mumol/l DA), but showed no mediolateral variation in either region. Peak DA efflux evoked by 25P/50 Hz relative to 1P efflux also varied between the two regions; the aCPu contained predominantly low ratio (25P/50 Hz: 1P) sites ranging from 1.47 to 3.71, whereas in the pCPu these ratios were higher, ranging from 2.73 to 9.40, and were particularly high in the dorsomedial region of the pCPu. Efflux detected in low ratio sites of the aCPu showed little dependence on the frequency (10 to 500 Hz), or the number of pulses (5 to 20) in a train. By contrast DA efflux evoked in high ratio sites of the pCPu responded in a pulse and frequency dependent manner, the maximum ratio (approximately 8 times 1P) being at 20P/20 Hz. Interestingly the frequency response relationship obtained in the pCPu resembled the profile observed in the nucleus accumbens (NAc). Voltammetric evidence and experiments with selective reuptake blockers indicated that only DA was measured in our studies and 5-HT did not significantly contribute to the frequency dependent pattern of efflux detected in high ratio sites of the pCPu, where striatal 5-HT concentrations are highest. Experiments with the selective D2 receptor antagonists metoclopramide or (-)sulpiride revealed that under our experimental conditions, DA efflux in the aCPu was not modulated by DA autoreceptor activation. By contrast, autoreceptor modulation did occur in high ratio sites of the pCPu at stimulations lasting longer than approximately 1000 ms. These observations support the concept that the caudate putamen is heterogeneously organised with respect to the frequency characteristics of evoked DA release. The factors controlling frequency dependent release under these conditions may be a function of A10 innervation, since high ratio release sites occur in areas where the density of such innervation is greatest, for example, the dorsomedial pCPu. This is supported by the observation that high ratio release sites are also found in the NAc, which receives dopaminergic fibres predominantly from an A10 region.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of cathinone and amphetamine on the neurochemistry of dopamine in vivo

The effects of (−)cathinone, the primary psyehoactive alkaloid of the Khat plant, were compared to those of (+)amphetamine in the anterior caudate-putamen and the nucleus accumbens. In vivo microdialysis was used to measure extracellular levels of dopamine and metabolites in both regions of the brain simultaneously, after intraperitoneal administration of 0.8, 1.6 or 3.2 mg/kg of either drug (doses expressed as the salts). Both drugs increased levels of dopamine but decreased levels of metabolites in a dose-dependent manner. However, the relative magnitude of these effects depended upon the specific drug, the dose and area of the brain examined. At the largest dose used, amphetamine had a relatively greater effect than cathinone on dopamine in both caudate and accumbens. However, among smaller doses, this difference was only observed in the nucleus accumbens after administration of 1.6 mg/kg. The results also demonstrated a differential regional effect of both drugs at 3.2 mg/kg, in that both had a greater effect on dopamine in the caudate, as opposed to the accumbens. These findings demonstrate a functional heterogeneity of the striatum of the rat, that may be relevant to the understanding of both normal brain function and the neural responses to psychoactive drugs.

Excitatory amino acid projections to the nucleus accumbens septi in the rat: A retrograde transport study utilizing d[ 3H]aspartate and [ 3H]GABA

Afferents to the nucleus accumbens septi utilizing glutamate or aspartate have been investigated in the rat by autoradiography following injection and retrograde transport of d[ 3H]aspartate. Parallel experiments with the intra-accumbal injection of [ 3H]GABA were employed to establish the transmitterselective nature of the retrograde labelling found with d[ 3H]aspartate. The topography of cortical and thalamic perikarya labelled by d[ 3H]aspartate was extremely precise. d[ 3H]Aspartate labelled perikarya were found in layer V of agranular insular cortex; bilaterally within prelimbic and infralimbic subareas perikarya, but predominantly ipsilaterally. Ipsilateral labelling was observed in dorsal, ventral and posterior agranular insular cortices, and in perirhinal cortex. Injections into ventral accumbens labelled perikarya in ipsilateral entorhinal cortex, while infusion of d[ 3H]aspartate into anterior caudate-putamen resulted in labelling of perikarya in ipsilateral cingulate and lateral precentral cortices. Following infusion of d[ 3H]aspartate, ipsilateral midline thalamic nuclei contained the highest density of labelled perikarya; infusions centred on nucleus accumbens resulted in heavy retrograde labelling of the parataenial nucleus, but labelling was sparse from a lateral site and not observed after injection into anterior caudate-putamen. Less prominent labelling of perikarya was seen in other thalamic nuclei (mediodorsal, central medial, rhomboid, reuniens and centrolateral), mostly near the midline. Perikaryal labelling was also found in the ipsilateral amygdaloid complex, particularly in basolateral and lateral nuclei. Only weak labelling resulted in ventral subiculum. Numerous labelled cells were present bilaterally in anterior olfactory nucleus, although perikarya were more prominent ipsilaterally. Labelled perikarya were not consistently observed in other regions (ventral tegmental area, medial substantia nigra, raphe nuclei and locus coeruleus) known to innervate nucleus accumbens. Presumptive anterograde labelling was detected in ventral pallidum/substantia innominata, ventral tegmental area and medial substantia nigra. [ 3H]GABA was generally not retrogradely transported to the same regions labelled by d[ 3H]aspartate; an exception being the anterior olfactory nucleus, where large numbers of labelled perikarya were found. [ 3H]GABA failed to label perikarya in thalamus and amygdala, and a topographic distribution of label was absent in neocortex. Overall our findings confirm the selectivity of the retrograde transport of d[ 3H]aspartate and [ 3H]GABA, and provide the first evidence that thalamic and amygdaloid afferents to nucleus accumbens utilize glutamate and/or aspartate as their transmitter. They also confirm previous evidence that corticofugal afferents to nucleus accumbens utilize an excitatory amino acid. Afferents from anterior olfactory nucleus to nucleus accumbens have not been previously described.

Estradiol suppresses then enhances intracaudate dopamine-induced contralateral deviation

The effects of estradiol on the amount of contralateral postural deviation elicited by unilateral intracaudate injection of dopamine (DA) were tested 2 days and 6 days after hormone treatment. DA (25 μg/0.25 μl) or a control vehicle solution (VH, 0.25 μl) was injected unilaterally into the dorsal anterior caudate-putamen of intact male rats and postural deviation was measured. Then, rats were given estradiol benzoate (EB, 50 μg/100 g body wt per 0.05 ml) or the vehicle, peanut oil (OIL, 0.05 ml/100 g body wt) once. At 2 days and 6 days after EB or OIL treatment, the rats were again administered DA or VH intrastriataly and the amount of contralateral postural deviation was measured. At 2 days after EB treatment the response to intrastriatal DA was significantly decreased, but by 6 days it was significantly increased; OIL had no effect. Thus, the behavioral effects of estrogen are time-dependent and may affect the postsynaptic response to DA in the striatum.

Circling behaviour following unilateral kainic acid injections into rat striatum

Unilateral injection of kainic acid (2,5–25 nmol) into rat anterior caudate-putamen induced dose-related circling behaviour. Kainic acid (10 nmol) consistently caused initial weak ipsiversive circling lasting 1 h followed by prolonged strong contraversive rotation lasting in excess of 10 h. Unilateral intrastriatal administration of L-glutamic acid, or of monosodium L-glutamate, to normal rats, or administration of monosodium L-glutamate to rats with extensive decortication, did not induce circling behaviour. The simultaneous unilateral injection of monosodium L-glutamate (1 μ mol) with kainic acid (10 nmol)_did not modify circling behaviour induced by kainic acid. However, extensive decortication greatly reduced circling induced by unilateral instratriatal kainic acid (10 nmol), an effect not reversed by the simultaneous administration of monosodium L-glutamate (1 μ mol). Unilateral 6-hydroxydopamine lesions of the left nigrostriatal pathway abolished the initial ipsiversive rotation and potentiated the subsequent contraversive rotation for u p to 4 h after intrastriatal injection of kainic acid (10 nmol). Peripheral administration of haloperidol (1 mg/kg i.p.) also abolished initial ipsiversive rotation and decreased the subsequent contraversive rotation. Electro-coagulation of the ipsilateral strio-nigral pathway prolonged the initial ipsiversive rotation produced by kainic acid, but markedly attenuated contraversive rotation. These findings suggest that circling induced by intrastriatal administration of kainic acid depends on intact corticostriate pathways, but it cannot be reproduced or modified by intrastriatal administration of glutamate. Kainic acid circling appears to be mediated via strio-nigral pathways, and to be modulated by dopaminergic function.

The induction of catalepsy and hyperactivity by morphine administered directly into the nucleus accumbens of rats

The injection of morphine (1–100 μg) into the nucleus accumbens of the rat caused dose-dependent changes in motor function. An initial cataleptic phase was followed by hyperactivity which was associated with a weak and periodic biting behaviour. Injection of morphine (1–50 μg) into associated brain areas (anterior and posterior regions of the olfactory tubercle, anterior caudate putamen, area preoptica, globus pallidus and ventricular system) failed to induce catalepsy or induce a catalepsy of comparable intensity to that observed after intra-accumbens morphine. The catalepsy induced by 12.5 or 50 μg intra-accumbens morphine was antagonised by nalorphine when administered s.c. (2.5–10 mg/kg) and by nalorphine (2.5–10 μg)_and naloxone (0.25–1.0 μg) when injected into the nucleus accumbens, by low doses of cyproheptadine (1.25–5 mg/kg i.p.) and by large and probably non-specific doses of atropine (10 mg/kg i.p.) and piperoxan (20 mg/kg i.p.). In relatively large doses haloperidol (0.25–1.0 mg/kg i.p.) potentiated morphine (3.125 μg) catalepsy whereas α-methylparatyrosine reduced or failed to modify the morphine (1–50 μg) response. It is considered that the catalepsy induced by intra-accumbens morphine is due to a significant action within that nucleus which directly or indirectly involves an enhanced serotonergic activity. The subsequent hyperactivity phase induced by intra-accumbens morphine was markedly reduced by α-methyl-p-tyrosine pretreatment (250 mg/kg i.p.) and the biting component was abolished. The hyperactivity was more sensitive to the antagonistic action of α-adrenoceptor blocking agents piperoxan (10–40 mg/kg i.p.), aceperone (1.25–20 mg/kg i.p.), piperoxan (6.25–25 μg intra-accumbens) and phentolamine (1.25– 10 μg intra-accumbens) than fluphenazine (1.25–2.5 mg/kg i.p.), whilst the biting was inhibited by both the α-adrenoceptor blocking agents and fluphenazine. These data suggest that whereas the hyperactivity induced by intra-accumbens morphine primarily involves an enhanced noradrenergic action, the biting effect involves both noradrenaline and dopamine. However, it is uncertain as to whether mechanisms within the nucleus accumbens or associated areas are primarily or jointly involved as substrates for this effect, for whilst injections of morphine (1–50 μg)_into the anterior alfactory tubercle failed to induce hyperactivity, injections into the anterior caudata putamen and globus pallidus evoked a weak response, and injections into the posterior olfactory tubercle and area preoptica induced marked hyperactivity associated with weak biting. An assessment of the diffusion of (N-methyl- 14C)-morphine on intra-accumbens injection, and particularly at the time when the hyperactivity phase was apparent indicated an ability to reach and more speculatively influence other than brain areas. This would emphasise that an extra-accumbens site of action for the mediation of the hyperactivity/biting effects cannot be excluded. The results indicate a differential involvement of forebrain structures with the biphasic motor behaviour induced by intracerebral injections of morphine and a usefulness of this agent to investigate the mechanisms involved in motor control.