Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism.

The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the striatum but it was less marked and shorter-lasting. At 10 mg/kg (i.p.), tianeptine significantly raised the extracellular concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in both regions. The effect of 10 mg/kg tianeptine on dopamine and its metabolites was not significantly changed in animals which had received this dose twice daily for 15 days. Intracerebroventricular administration of 150 micrograms/20 microliters 5,7-dihydroxytryptamine, which markedly depleted serotonin in the brain, did not modify the effect of 10 mg/kg tianeptine on the extracellular concentrations of dopamine and HVA in the nucleus accumbens but reduced the effect on DOPAC. Various doses of tianeptine (1, 3 and 10 mg/kg i.p.) did not change the synthesis of serotonin and dopamine in the striatum and nucleus accumbens. The results show that tianeptine increased the extracellular concentrations of dopamine more in the nucleus accumbens than in striatum. The effect on the output of DA in the nucleus accumbens could be involved in the antidepressant activity of tianeptine.     

R-(+)-HA-966, a glycine/NMDA receptor antagonist, selectively blocks the activation of the mesolimbic dopamine system by amphetamine.

1. The effects of the glycine/NMDA receptor antagonist, (+)-HA-966 on the neurochemical and behavioural responses to amphetamine have been determined in the mouse and rat. 2. In vehicle-treated control mice, (+)-HA-966 (30-100 mg kg-1) did not affect dopamine synthesis in either the nucleus accumbens or striatum and was without marked effect on spontaneous locomotor activity. 3. In the mouse, (+)-HA-966 (30 and 100 mg kg-1) dose-dependently blocked the enhancement of dopamine synthesis induced in the nucleus accumbens by amphetamine, but was without effect on the increase in dopamine synthesis in the striatum. 4. Intracerebroventricular administration of the glycine/NMDA receptor antagonist, 5,7-dichlorokynurenic acid, in the mouse (10 micrograms) also significantly attenuated amphetamine-enhanced DOPA accumulation in the nucleus accumbens, but not in the striatum. 5. The decrease of dopamine synthesis in striatum and nucleus accumbens induced by the dopamine receptor agonist, apomorphine, was unaffected by (+)-HA-966 (100 mg kg-1). 6. (+)-HA-966 (30 mg kg-1) failed to attenuate the hyperactivity induced by the systemic administration of amphetamine in the mouse, but totally prevented the hyperlocomotion following infusion of amphetamine into the rat nucleus accumbens. In contrast, stereotyped behaviour induced by infusion of amphetamine into the rat striatum was not altered following pretreatment with (+)-HA-966 (30 mg kg-1). 7. The results are consistent with a selective facilitatory role of glycine/NMDA receptors on mesolimbic dopaminergic neurones.     

Activation of mesolimbic dopaminergic neurons following central administration of histamine is mediated by H1 receptors

Summary The effect of intracerebroventricular administration of histamine on the activity of mesolimbic and nigrostriatal dopaminergic (DA) neurons was determined in male rats. The activity of these neurons was estimated by measuring: (1) the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after administration of a decarboxylase inhibitor, and (2) the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and striatum, which contain the terminals of these neurons. Central administration of histamine increased both DOPA accumulation and DOPAC concentrations in the nucleus accumbens, but was without effect in the striatum. The increase in DOPAC concentrations in the nucleus accumbens occurred within 10 min and was sustained for at least 120 min. The H₁ antagonist mepyramine blocked whereas the H₂ antagonist zolantidine did not affect histamine-induced increases in DOPAC concentrations in the nucleus accumbens. Neither mepyramine nor zolantidine affected basal DOPAC concentrations in the nucleus accumbens. These results indicate that central administration of histamine stimulates mesolimbic DA neurons through an action at the H₁ receptor, but has no effect upon the activity of nigrostriatal DA neurons.Correspondence to A. E. Fleckenstein at the above address     

Acute administration of clozapine, thioridazine and metoclopramide increases extracellular DOPAC and decreases extracellular 5-HIAA, measured in the nucleus accumbens and striatum of the rat using in vivo voltammetry

Changes in the extracellular levels of dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-indoleacetic acid (5-HIAA) after acute administration of clozapine (50 mg/kg s.c.), thioridazine (20 mg/kg s.c.) and metoclopramide (5 mg/kg s.c.), were monitored using in vivo voltammetry with micro-carbon electrodes implanted in the nucleus accumbens and striatum of the rat anaesthetised with halothane/N2O. Both clozapine and thioridazine increased extracellular levels of DOPAC in the striatum and the nucleus accumbens. The maximum increases with clozapine were 60% and 86% in the nucleus accumbens and striatum and 44% and 55% with thioridazine. Both neuroleptics also decreased the extracellular level of 5-HIAA in these regions of the brain. Metoclopramide increased the extracellular level of DOPAC in the nucleus accumbens (42%) and the striatum (57%) and significantly decreased the level of 5-HIAA in the nucleus accumbens. These results suggest that the two so-called atypical neuroleptics, clozapine and thioridazine, do not have selective effects on the metabolism of dopamine in vivo in the nucleus accumbens after acute administration. Furthermore, neuroleptic-induced increases in dopamine metabolism are accompanied by reciprocal decreases in 5-hydroxytryptamine metabolism in vivo.     

Dopamine in the basal ganglia and benzodiazepine-induced sedation

The effects of the anxiolytic benzodiazepine flurazepam on motor activity and the turnover of dopamine were measured in rats. Changes in motor activity were measured using a doppler-shift device; changes in extracellular homovanillic acid (HVA), monitored by linear sweep voltammetry with carbon paste electrodes implanted in the striatum and nucleus accumbens and ex vivo measurements of changes in 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios in the striatum and nucleus accumbens were used as indices of changes in the turnover of dopamine. Injection of vehicle increased the nocturnal rise in the concentration of HVA and the ex vivo DOPAC/DA ratio in the nucleus accumbens. Injection of flurazepam decreased the nocturnal rise in HVA and DOPAC/DA ratio in the nucleus accumbens below control levels. There was also a decrease in the nocturnal rise in motor activity. Neither injection of vehicle nor injection of flurazepam caused changes in either the concentration of HVA or the DOPAC/DA ratio in the striatum. The correlation coefficient for motor activity compared to concentration of HVA remained high for the nucleus accumbens but was reduced for the striatum after administration of flurazepam. The results suggest that the sedative effect of flurazepam may be due to an action on the mesolimbic but not the nigrostriatal dopaminergic pathway.     

Effect of neurotensin, substance P and TRH on the regulation of dopamine receptors in rat brain

Rats were exposed for one week to either neurotensin (4 micrograms/h), substance P (3.3 micrograms/h), thyrotropin-releasing hormone (5 micrograms/h), or saline administered intracerebroventricularly via mini osmotic-pumps and either haloperidol (2.5 mg/kg i.p., 2 X daily) or vehicle control. The peptide treatments by themselves did not alter [3H]spiroperidol binding in either the nucleus accumbens or the striatum. Neurotensin, however, augmented the increase in [3H]spiroperidol binding caused by the haloperidol treatment in both the nucleus accumbens and striatum.     

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain.

1. The effects of single-dose regimens of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine (DA) release and metabolism were evaluated in the frontal cortex, hypothalamus, nucleus accumbens and striatum. The regimens selected are known to produce substantial behavioural effects. 2. 3-Methoxytyramine (3MT) and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were used to assess DA metabolism by catechol-O-methyltransferase and monoamine oxidase respectively. The rate of formation of 3MT was used as an index of synaptic DA. The ratio and sum, respectively, of 3MT and DOPAC rates of formation were used to assess DA reuptake inhibition and turnover. 3. The effects of amphetamine on 3MT production and DOPAC steady-state levels were similar in all regions, suggesting similar pharmacodynamic actions. Amphetamine increased 3MT formation and steady-state levels, and reduced DOPAC steady-state levels. DOPAC formation was significantly reduced only in the nucleus accumbens and striatum. Total DA turnover remained unchanged except in the nucleus accumbens. Apparently, the amphetamine-induced increase in DA release occurred at the expense of intraneuronal DA metabolism and did not require stimulation of synthesis. 4. Nomifensine elevated 3MT formation in all regions. A similar effect was produced by cocaine except in the nucleus accumbens. GBR 12909 elevated 3MT production only in the hypothalamus, the striatum and the nucleus accumbens. 5. Cocaine selectively reduced DOPAC formation in the frontal cortex. Nomifensine increased and reduced, respectively, DOPAC formation in striatum and hypothalamus. GBR 12909 elevated DOPAC formation in all regions except the cortex, where pargyline did not reduce DOPAC levels in GBR 12909-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Repeated atypical neuroleptic administration: effects on central dopamine metabolism monitored by in vivo voltammetry

Changes in extracellular DOPAC levels were monitored simultaneously in the nucleus accumbens and striatum of halothane/N2O anaesthetised rats using in vivo differential pulse voltammetry with carbon fibre electrodes following repeated administration of the atypical neuroleptics thioridazine and clozapine. Thioridazine (20 mg/kg s.c.) increased the DOPAC peak in the nucleus accumbens and striatum of rats treated with saline for the previous 21 days by 66% +/- 5 S.E.M. and 91% +/- 16 respectively. No such increase was recorded in the nucleus accumbens of rats previously treated with thioridazine (20 mg/kg s.c.) for 21 days. Similarly the increase in the striatum produced by a challenge dose on day 22 was markedly attenuated compared to controls although analysis of absolute DOPAC peak heights revealed extracellular DOPAC to be elevated above basal levels in this region (but not the nucleus accumbens) indicating a possible selective action of this drug to induce absolute tolerance to its acute effects in the nucleus accumbens after repeated administration. Administration of increasing doses of apomorphine (0.05, 0.1, 0.25 mg/kg s.c.) 1 h after a challenge dose of thioridazine (20 mg/kg s.c.) on day 22 to rats treated with the neuroleptic for the previous 21 days produced a progressive decrease in extracellular DOPAC levels both in the nucleus accumbens and striatum. Repeated administration of clozapine (50 mg/kg s.c.) for 21 days failed to induce tolerance to the acute effects of this drug, extracellular DOPAC levels increasing by 60% +/- 8 and 90% +/- 18 in the nucleus accumbens and striatum respectively following challenge with the drug on day 22.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local administration of flurazepam has different effects on dopamine release in striatum and nucleus accumbens: a microdialysis study

The action of local administration of flurazepam on extracellular levels of dopamine (DA) and its metabolites 3,4 dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the anterior striatum and medial nucleus accumbens have been investigated using microdialysis. Flurazepam (10 microM), administered through the perfusion medium for 20 min, reduced levels of DA in dialysates from the nucleus accumbens by 60% while the same concentration of the drug had no effect on levels of DA in perfusates from the striatum. Pretreatment with the benzodiazepine antagonist Ro 15-1788 (flumazenil) or with picrotoxin, a drug which blocks the GABAA receptor-associated chloride channel, inhibited the effect of flurazepam on levels of DA in the nucleus accumbens, which suggests that the effect was mediated by the multimolecular GABAA/benzodiazepine receptor complex. Administration of flurazepam had little effect on the two metabolites of DA, DOPAC and HVA, in either the nucleus accumbens or striatum. The inverse partial benzodiazepine agonist, FG 7142, had no significant action on the release of DA in the nucleus accumbens. These results suggest that the dopaminergic projection to the nucleus accumbens is more sensitive to benzodiazepine-induced inhibition than the projection to the striatum.     

The TRH analogue CG3509 increases in vivo catechol/ascorbate oxidation in the N. accumbens but not in the striatum of the rat

The effects of injection of the thyrotrophin-releasing hormone (TRH) analogue, orotyl-histidyl-proline amide (CG3509) into the accumbens and striatum, was studied on dopamine metabolism by means of in vivo voltammetry. Forty minutes after infusion of CG3509 (1-5 micrograms) into the n. accumbens there was a significant dose-related increase in the oxidation peak, corresponding to the oxidation of the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC) and ascorbic acid. The size of this peak returned to normal by 80 min after the infusion. There was no change in the indole oxidation peak. Infusion of CG3509 (5 micrograms) had no effect on the size of either the catechol or the indole oxidation peaks recorded in the striatum. Intraventricular injection of CG3509 (10 micrograms) also increased DOPAC/ascorbic acid oxidation peak recorded in the n. accumbens, without altering the indole peak. While the voltammetric technique used in the present experiments is not able fully to separate ascorbic acid and DOPAC in vivo, the results support the view that TRH and its analogues selectively increase dopaminergic activity in the mesolimbic region.     

Release of dopamine is reduced by diazepam more in the nucleus accumbens than in the caudate nucleus of conscious rats

The effects of 1-20 mg/kg diazepam were studied on the extracellular concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and striatum of conscious rats, using intracerebral microdialysis. Five, but not 1 mg/kg diazepam significantly reduced extracellular DA, DOPAC and HVA in the nucleus accumbens. Twenty mg/kg diazepam significantly reduced extracellular DA, DOPAC and HVA in the striatum. A significant effect on striatal DOPAC, but not on DA and HVA, was seen with 10 mg/kg diazepam, while no changes were found with 5 mg/kg diazepam. The results suggest that diazepam reduces the release and metabolism of DA in the nucleus accumbens more than in the striatum.     

NMDA antagonists block restraint-induced increase in extracellular DOPAC in rat nucleus accumbens

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonists CPP, TCP, PK 26124 and ifenprodil, and of the minor tranquillizer diazepam on stress-induced changes of dopamine metabolism in the nucleus accumbens were investigated in the rat. Dopamine metabolism was assessed by measuring the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) by means of in vivo differential pulse voltammetry with electrochemically pretreated carbon fiber electrodes. Physical immobilization of the rats for 4 min caused a marked and long-lasting increase in extracellular DOPAC levels in the nucleus accumbens. A similar, though shorter-lasting, augmentation of extracellular DOPAC was observed in the nucleus accumbens after systemic administration of the anxiogenic agent methyl-beta-carboline-3-carboxylate (beta-CCM) (10 mg/kg s.c.). Pretreatment with CPP (1 mg/kg i.p.), TCP (3 mg/kg i.p.), PK 26124 (3 mg/kg i.p.), ifenprodil (3 mg/kg i.p.) or diazepam (2 mg/kg i.p.) totally antagonized the immobilization-induced increase in extracellular DOPAC in the nucleus accumbens. Diazepam and the benzodiazepine (omega 1-2) receptor antagonist flumazenil (30 mg/kg i.p.), but not ifenprodil, also antagonized the beta-CCM-induced activation of dopamine metabolism in the nucleus accumbens. Finally, systemic administration of haloperidol (25 micrograms/kg i.p.) increased the extracellular concentrations of DOPAC in the nucleus accumbens, but pretreatment with ifenprodil (3 mg/kg i.p.) did not modify this response. These data indicate that NMDA receptor antagonists prevent the activation of dopamine metabolism in the nucleus accumbens caused by immobilization stress but not by beta-CCM-induced anxiogenic stimulation. These results suggest that NMDA receptor antagonists may possess an anxiolytic-like action in the rodent, which is exerted via neuroanatomical circuits distinct from those acted upon by diazepam.     

5-HT3 Receptor Antagonist MDL 72222 Dose-Dependently Attenuates Cocaine- and Amphetamine-Induced Elevations of Extracellular Dopamine in the Nucleus Accumbens and the Dorsal Striatum

Abstract: The effects of a 5-HT₃ receptor antagonist MDL 72222 on cocaine- and amphetamine-induced increases in extracellular dopamine in the nucleus accumbens and the dorsal striatum were studied with microdialysis technique using halothane anaesthesized rats. Dopamine and its metabolites were measured by HPLC with electrochemical detection. Cocaine elevated extracellular dopamine in the nucleus accumbens and to a lesser extent in the dorsal striatum, but it did not affect dopamine metabolites, 3 ,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid. Pretreatment with MDL 72222 (25-100 μg/kg) dose-dependently attenuated cocaine-induced elevation of dopamine in both of the nuclei studied. Amphetamine elevated extracellular dopamine and reduced DOPAC and homovanillic acid equally in the nucleus accumbens and in the dorsal striatum. MDL 72222 also attenuated the amphetamine-induced elevation of extracellular dopamine concentration in both brain areas studied, but first at a dose of 100 μg/kg. The different potencies of the interactions of the 5-HT₃ receptor antagonist with cocaine and amphetamine could be related to the different mechanisms by which these drugs primarily elevate extracellular dopamine.     

Modulation of mesolimbic dopaminergic projections by beta-endorphin in the rat

Intracerebroventricular injection of beta-endorphin stimulated the metabolism of dopamine in a dose-dependent, opiate antagonist-reversible manner. Local injections into the nucleus accumbens also caused similar increases, indicating that the actions of this peptide on mesolimbic dopaminergic projections were occurring at opioid receptor sites within the nucleus accumbens. Tolerance experiments suggested that epsilon opioid receptors may be involved in mediating these effects in the n. accumbens, unlike in the striatum.     

Pharmacokinetics of morphine in striatum and nucleus accumbens: relationship to pharmacological actions

The pharmacokinetics of morphine was compared with its ability to increase striatal dopamine turnover (estimated by an increase in DOPAC concentration) and to produce the development of a muscular rigidity (estimated as a tonic activity in the electromyogram). After systemic administration of morphine (15 mg/kg IP), the concentration of morphine in blood plasma, striatum and substantia nigra showed a parallel time course with a maximum after 30 min; in the striatum, in addition, normorphine was found in a lower concentration, but with a similar time course. The elevation of striatal DOPAC, in contrast, commenced very rapidly and lasted for about four hours. The rigidity appeared later and disappeared earlier than the striatal DOPAC elevation. After unilateral intrastriatal injection of morphine (15 micrograms), a small amount of the drug penetrated very rapidly to distant sites, such as the contralateral striatum and nucleus accumbens, as well as to the ipsilateral nucleus accumbens. The results suggest that the relationship between pharmacokinetics and pharmacodynamics of morphine, both after systemic and after local injection into the brain, is more complex than could be expected from previous findings.     

SB 242084, a selective serotonin2C receptor antagonist, increases dopaminergic transmission in the mesolimbic system.

Electrophysiological techniques and in vivo microdialysis were used to investigate the effect of SB 242084, a potent and selective 5-HT2C receptor antagonist in the control of nigro-striatal and mesolimbic dopaminergic function. Thus, extracellular single unit recordings were performed from neurochemically-identified dopamine (DA) neurons in the substantia nigra, pars compacta (SNc) and the ventral tegmental area (VTA), as well as monitoring of striatal and accumbal basal DA release in anesthetized rats following the administration of SB 242084 and RO 60-0175. Administration of SB 242084 (160-640 microg/kg, i.v.) caused a dose-dependent increase in the basal firing rate of VTA DA neurons, reaching its maximum (27.8+/-6%, above baseline) after 640 microg/kg. Moreover, bursting activity was significantly enhanced by SB 242084 in the VTA. On the other hand, SB 242084 (160-640 microg/kg, i.v.) did not cause any significant change in the basal firing rate and bursting activity of DA neurons in the SNc. Injection of the 5-HT2C receptor agonist RO 60-0175 (80-320% microg/kg, i.v.) dose-dependently decreased the basal firing of DA neurons in the VTA but not in the SNc. RO 60-0175 exerted its maximal inhibitory effect (53.9+/-15.1%, below baseline) in the VTA at the dose of 320 microg/kg. Basal DA release (34.8+/-9%, above baseline) and dihydroxyphenylacetic acid (DOPAC) efflux (19.7+/-7%, above baseline) were significantly enhanced in the nucleus accumbens following the intraperitoneal administration of 10 mg/kg SB 242084. Intraperitoneal injection of 5 mg/kg SB 242084 significantly increased DA release (16.4+/-6%, above baseline) in the nucleus accumbens, but did not affect DOPAC efflux. In the striatum, SB 242084 (5 and 10 mg/kg, i.p.) only slightly increased DA release above baseline (3.5+/-4 and 11.2+/-6%, respectively), without affecting DOPAC efflux in this area. However, the effect of SB 242084 in the striatum was rendered more evident by the fact that injection of the vehicle used to dissolve the drug in a group of control rats, significantly reduced basal DA output by 19.6+/-7%. Stimulation of 5-HT2C receptors by RO 60-0175 (1 mg/kg, i.p.) significantly decreased DA release in the nucleus accumbens by 26.1+/-4% (below baseline) 60 min after injection. On the other hand, RO 60-0175 (1 mg/kg, i.p.) did not cause any significant change of DA release in the striatum. However, DOPAC efflux was reduced by RO 60-0175 (1 mg/kg, i.p.) both in the striatum and the nucleus accumbens. Taken together, these data indicate that the central 5-HT system exerts a tonic and phasic inhibitory control on mesolimbic DA neuron activity and that 5-HT2C receptor subtypes are involved in this effect. Moreover, these findings might open new possibilities for the employment of 5-HT2C receptor antagonists in the treatment of neuropsychiatric disorders related to a hypofunction of central DA neurons.     

Role of dopamine D-1 and D-2 receptors in the regulation of neurotensin systems of the neostriatum and the nucleus accumbens

Activation of dopamine D-1 receptors with multiple administrations of SKF 38393 significantly increased the level of neurotensin-like immunoreactivity in the striatum and the nucleus accumbens. However, a similar treatment with the D-2 receptor-selective agonist, LY 171555, decreased the same in both structures; when the two drugs were administered concureently, their individual effects were blocked. These results suggest that dopamine D-1 and D-2 receptors antagonistically regulate neurotensin systems of the striatum and nucleus accumbens. On the other hand, blockade of D-2 receptors (with sulpiride) elevated, while D-1 receptors blockade (with SCH 23390) caused no change in the level of neurotensin in both these structures. Dopamine D-1 receptors did not appear to contribute to the sulpiride-mediated effect as concurrent administration of SCH 23390 did not alter the response.     

Acute effects of D-1 and D-2 dopamine receptor agonist and antagonist drugs on basal ganglia [Met5]- and [Leu5]-enkephalin and neurotensin content in the rat.

The effects of acute systemic injection of the D-1 agonist SKF 38393 (2.5-20 mg/kg) or the D-1 antagonist SCH 23390 (0.25-2.0 mg/kg), and of the D-2 agonist quinpirole (0.12-1.0 mg/kg) or the D-2 antagonist sulpiride (25-100 mg/kg) on the neuropeptide content of rat basal ganglia were investigated. In striatum, the [Met5]- and [Leu5]-enkephalin content was unaffected by administration of SKF 38393 or SCH 23390. Quinpirole had no effect on [Met5]- and [Leu5]-enkephalin levels but sulpiride produced an increase in both [Met5]- and [Leu5]-enkephalin content. In the nucleus accumbens, SKF 38393 decreased and SCH 23390 increased [Met5]- and [Leu5]enkephalin levels. Quinpirole decreased [Met5]- and [Leu5]-enkephalin levels, while sulpiride decreased [Leu5]-enkephalin levels alone. The content of [Leu5]- but not [Met5]-enkephalin levels in the substantia nigra was increased by administration of SKF 38393, and decreased by SCH 23390. Quinpirole and sulpiride were without effect on the [Met5]- or [Leu5]-enkephalin content of substantia nigra. Neurotensin levels in striatum were increased by administration of SKF 38393 and decreased by SCH 23390. Similarly, quinpirole decreased the neurotensin content while sulpiride caused an increase. In the nucleus accumbens, the neurotensin content was not affected by administration of SKF 38393 but increased by SCH 23390. Neither quinpirole nor sulpiride altered neurotensin levels in the nucleus accumbens. Neurotensin levels in substantia nigra were unaffected by the administration of SKF 38393 and SCH 23390, or by quinpirole and sulpiride. These results indicate that acute administration of D-1 and D-2 agonist and antagonist drugs can alter the levels of [Met5]- and [Leu5]-enkephalin and neurotensin in basal ganglia. However, there are marked differences between brain regions in the regulation of peptide levels by acute D-1 and D-2 receptor occupation.