Seed traits and germination behaviour of four Sardinian populations of Helichrysum microphyllum subsp. tyrrhenicum (Asteraceae) along an altitudinal gradient.

Helichrysum microphyllum subsp. tyrrhenicum (Asteraceae) is an endemic taxon of Sardinia and Corsica, where it grows at different altitudes. The objective of this study was to investigate the seed traits and germination behaviour of four Sardinian populations of this taxon located at different altitudes. Seed traits were evaluated, and germination tests were carried out by incubating seeds at a range of constant (5-30 °C) and alternating (25/10 °C) temperatures. The dry after-ripening (DAR) pre-treatment was also applied by storing seed in dry conditions for 3 months at 25 °C. Seed traits and germination behaviour data were statistically analysed to identify if there was a correlation with altitude. Differences in seed size, area and mass among populations were recorded, however, no relationship was found with altitude. High germination percentages were obtained in all populations, both in untreated and DAR seeds, and were positively affected by alternating temperatures. The final germination percentage and time required to reach 50% final germination (T50 ) showed no relationship with altitude. The differences in seed traits and germination detected among the studied populations of H. microphyllum subsp. tyrrhenicum were not correlated with altitude. This study provides new and important knowledge for this taxon. H. microphyllum subsp. tyrrhenicum is characterised by high germination percentages and low T50 values and does not seem to require any dormancy-breaking treatment. This species represents a high-potential native plant species that should be considered within environmental management plans.

Metal Tolerance Capability of Helichrysum microphyllum Cambess. subsp. tyrrhenicum Bacch., Brullo & Giusso: A Candidate for Phytostabilization in Abandoned Mine Sites.

Sardinia was known as an important mine pole in Europe during his history. Still after decades from mine closure, 75.000.000 m3 of mine waste, rich in heavy metals, were left abandoned causing a huge environmental legacy on the mine district area. Consequently, cost effective remediation is required. In this frame, phytoremediation is considered a feasible candidate. This research was focused on Helichrysum microphyllum subsp. tyrrhenicum, which is pioneer in xeric soils with low-functions, like mine tailings. The aim of this study was to evaluate its ability to extract heavy metals from mine soils and accumulate them in plant tissues and its suitability for phytostabilization. Sundry samples of soil, roots and epigean organ were collected through field sampling and analysed in order to obtain metals concentration and mineralogical characteristics. Our results indicate that this species tolerates high concentration of zinc, lead and cadmium, behaving as a species suitable for phytostabilization.

Dissecting seed dormancy and germination in Aquilegia barbaricina, through thermal kinetics of embryo growth.

Threshold-based thermal time models provide insight into the physiological switch from the dormant to the non-dormant germinating seed. This approach was used to quantify the different growth responses of the embryo of seeds purported to have morphophysiological dormancy (MPD) through the complex phases of dormancy release and germination. Aquilegia barbaricina seeds were incubated at constant temperatures (10-25 °C) and 25/10 °C, without pre-treatment, after warm+cold stratification (W+C) and GA3 treatment. Embryo growth was assessed and the time of testa and endosperm rupture scored. Base temperatures (Tb ) and thermal times for 50% (θ50 ) of embryo growth and seed germination were calculated. W+C enabled slow embryo growth. W+C and GA3 promoted rapid embryo growth and subsequent radicle emergence. The embryo internal growth base temperature (Tbe ) was ca. 5 °C for W+C and GA3 -treated seeds. GA3 treatment also resulted in similar Tb estimates for radicle emergence. The thermal times for embryo growth (θe50 ) and germination (θg50 ) were four- to six-fold longer in the presence of GA3 compared to W+C. A. barbaricina is characterised by a multi-step seed germination. The slow embryo growth during W+C reflects continuation of the maternal programme of development, whilst the thermal kinetics of both embryo and radicle growth after the removal of physiological dormancy are distinctly different. The effects of W+C on the multiphasic germination response in MPD seeds are only partially mimicked by 250 mg·l-1 GA3 . The thermal time approach could be a valid tool to model thermal kinetics of embryo growth and radicle protrusion.

HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase.

The Trans-activator protein (Tat) of human immunodeficiency virus (HIV) is a pleiotropic protein involved in different aspects of AIDS pathogenesis. As a number of viral proteins Tat is suspected to disturb mitochondrial function. We prepared pure synthetic full-length Tat by native chemical ligation (NCL), and Tat peptides, to evaluate their direct effects on isolated mitochondria. Submicromolar doses of synthetic Tat cause a rapid dissipation of the mitochondrial transmembrane potential (ΔΨ(m)) as well as cytochrome c release in mitochondria isolated from mouse liver, heart, and brain. Accordingly, Tat decreases substrate oxidation by mitochondria isolated from these tissues, with oxygen uptake being initially restored by adding cytochrome c. The anion-channel inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) protects isolated mitochondria against Tat-induced mitochondrial membrane permeabilization (MMP), whereas ruthenium red, a ryanodine receptor blocker, does not. Pharmacologic inhibitors of the permeability transition pore, Bax/Bak inhibitors, and recombinant Bcl-2 and Bcl-XL proteins do not reduce Tat-induced MMP. We finally observed that Tat inhibits cytochrome c oxidase (COX) activity in disrupted mitochondria isolated from liver, heart, and brain of both mouse and human samples, making it the first described viral protein to be a potential COX inhibitor.

Interchangeable effects of gibberellic acid and temperature on embryo growth, seed germination and epicotyl emergence in Ribes multiflorum ssp. sandalioticum (Grossulariaceae).

Morphophysiological dormancy was investigated in seeds of Ribes multiflorum Kit ex Roem et Schult. ssp. sandalioticum Arrigoni, a rare mountain species endemic to Sardinia (Italy). There were no differences in imbibition rates between intact and scarified seeds, suggesting a lack of physical dormancy, while methylene blue solution (0.5%) highlighted a preferential pathway for solution entrance through the raphe. Embryos were small at seed dispersal, with an initial embryo:seed ratio (E:S) of ca. 0.2 (embryo length, ca. 0.5 mm), whereas the critical E:S ratio for germination was three times longer (ca. 0.6). Gibberellic acid (GA(3), 250 mg · l(-1)) and warm stratification (25 °C for 3 months) followed by low temperature (<15 °C) enhanced embryo growth rate (maximum of ca. 0.04 mm · day(-1) at 10 °C) and subsequent seed germination (radicle emergence; ca. 80% at 10 °C). Low germination occurred at warmer temperatures, and cold stratification (5 °C for 3 months) induced secondary dormancy. After radicle emergence, epicotyl emergence was delayed for ca. 2 months for seeds from three different populations. Mean time of epicotyl emergence was affected by GA(3) . Seeds of this species showed non-deep simple (root) - non-deep simple (epicotyl) morphophysiological dormancy, highlighting a high synchronisation with Mediterranean seasonality in all the investigated populations.

Enhancement of basal and pentylenetetrazol (PTZ)-stimulated dopamine release in the brain of freely moving rats by PTZ-induced kindling.

The effects of pentylenetetrazol (PTZ)-induced kindling on the activity of mesocortical, mesoaccumbens, and nigrostriatal dopaminergic neurons was investigated with the transversal microdialysis technique in freely moving rats. Four days after the last chronic administration of PTZ, the basal extracellular concentrations of dopamine in the prefrontal cortex, nucleus accumbens, and striatum of kindled rats were significantly increased (+76, +36, +49%, respectively) relative to those of animals chronically treated with saline. Moreover, dopamine output was markedly more sensitive to the effect of a challenge injection of PTZ (20 mg/kg ip) in the prefrontal cortex (+93 vs. +50%, relative to basal values), the nucleus accumbens (+36 vs. +4%), and the striatum (+50 vs. + 35%) of kindled rats relative to that in the control animals. Because kindled rats and their controls are habituated to handling, the neurochemical mechanisms that underlie the effects of chemical kindling on the sensitivity of dopaminergic neurons to PTZ were investigated by comparing the effects of an acute administration of PTZ (20 mg/kg ip) between naive and handling-habituated animals. The sensitivity of dopamine output to PTZ in naive rats was markedly greater than that in handling-habituated animals for the prefrontal cortex (+83 vs. +50%) and nucleus accumbens (+35 vs. +4%), but not for the striatum (+35 vs. +32%). These results indicate that PTZ kindling enhances the basal activity and the sensitivity to PTZ of dopamine neurons in rat brain and suggest that mesocortical, mesoaccumbens, and nigrostriatal dopaminergic neurons contribute to the central alterations associated with experimental epilepsy.

Enhancement by flumazenil of dopamine release in the nucleus accumbens of rats repeatedly exposed to diazepam or imidazenil.

The effect of long-term treatment (three times daily for 3 weeks) with a behaviorally relevant dose of the benzodiazepine receptor partial agonist imidazenil (0.5 mg/kg, IP) on basal dopamine release in the nucleus accumbens of freely moving rats was compared with that of diazepam (3 mg/kg, IP), a benzodiazepine receptor full agonist. Challenge doses of imidazenil and diazepam decreased the extracellular dopamine concentration in the nucleus accumbens by approximately the same extent in animals repeatedly exposed to vehicle or to the respective drug. Moreover, the abrupt discontinuation of long-term treatment with diazepam or imidazenil failed to affect basal dopamine release in this brain area during the first 5 days of withdrawal. In contrast, administration of the benzodiazepine receptor antagonist flumazenil (4 mg/kg, IP) elicited a marked increase (95 or 60%) in dopamine release in the nucleus accumbens 6 h after withdrawal of diazepam or imidazenil, respectively. Flumazenil induced a similar but smaller effect (50% increase) 5 days after diazepam withdrawal but had no effect 5 days after discontinuation of imidazenil treatment. The results support an involvement of the mesoaccumbens dopaminergic neurons in the withdrawal syndrome precipitated by flumazenil and allow further differentiation of benzodiazepine receptor partial and full agonists with respect to dependence liability of dopaminergic neurons in the nucleus accumbens.

Failure of chronic treatment with abecarnil to induce contigent and noncontingent tolerance in pentylenetetrazol-kindled rats.

We examined the effect of chronic treatment with abecarnil, a selective agonist at gamma-aminobutyric acid(A) (GABA(A)) receptors, on the development of tolerance to its anticonvulsant effect in pentylenetetrazole (PTZ)-kindled rats. We used two different experimental protocols to differentiate between pharmacological (noncontingent) and contingent tolerance. In one group of animals, kindling was suspended and abercarnil (1mg/kg intraperitoneally, i.p.) was administered three times daily for 15 days. In a second group of rats, PTZ-kindling was continued during chronic treatment with abecarnil. Tolerance to the anticonvulsant effect of a subsequent challenge dose of abecarnil (0.5 mg/kg i.p.) did not develop in either experimental group.

Inhibition of basal and stress-induced dopamine release in the cerebral cortex and nucleus accumbens of freely moving rats by the neurosteroid allopregnanolone.

The neurosteroid allopregnanolone is a potent and efficacious modulator of γ-aminobutyric acid (GABA) type A receptors. The effects of intracerebroventricular injection of allopregnanolone (5 to 15 µg in 5 µl) on basal and stress-induced changes in the extracellular concentrations of dopamine were investigated by microdialysis in various brain areas of freely moving rats and compared with those of the benzodiazepine midazolam (1 to 10 µg in 5 µl). Allopregnanolone reduced (by a maximum of 65 to 75%) basal dopamine content in the prefrontal cortex and nucleus accumbens in a dose-dependent manner, but had no effect on dopamine output in the striatum. Allopregnanolone (10 to 15 µg) also completely prevented the increase in extracellular dopamine concentrations in the nucleus accumbens and cerebral cortex induced by foot-shock stress. Midazolam reduced basal dopamine content in all three brain regions studied as well as the stress- induced increase in dopamine content in the nucleus accumbens and cerebral cortex with a greater potency than allopregnanolone. These results suggest that endogenous neurosteroids may participate in the GABAergic modulation of dopaminergic transmission in the rat cerebral cortex and nucleus accumbens, two brain areas which are important in the regulation of emotional processes. These agents do not appear to affect striatal dopaminergic transmission which modulates motor function.

Antagonism of isoniazid-induced convulsions by abecarnil in mice tolerant to diazepam.

The ability of the benzodiazepine receptor full agonist diazepam, the selective agonist abecarnil, and the partial agonist imidazenil to antagonize convulsions induced by isoniazid (200 mg/kg, S.C.) was studied in mice chronically treated with diazepam (3 mg/kg, i.p., three times daily) or abecarnil (0.1 or 1 mg/kg, i.p., three times daily or 6 mg/kg, S.C., daily). Diazepam induced tolerance to its own anticonvulsant effect. In contrast, chronic treatment with abecarnil failed to induce tolerance to its own anticonvulsant activity. Animals treated with abecarnil at 0.1 mg/kg developed cross-tolerance to imidazenil, whereas those treated with 1 mg/kg became less sensitive to diazepam. Mice chronically treated with abecarnil at 6 mg/kg showed almost complete tolerance to diazepam. Abecarnil was able to antagonize the convulsions elicited by isoniazid in diazepam-tolerant mice. These data indicate that chronic administration of abecarnil, unlike that of classical benzodiazepines, does not induce tolerance to its anticonvulsant effect, and that abecarnil overcomes tolerance induced by long-term treatment with the full agonist diazepam.

Proconflict effect of carbon dioxide inhalation in rats.

The effect of brief inhalation of carbon dioxide (CO2) was studied in a conflict situation (Vogel test) in the rat. This treatment, which inhibits gamma-aminobutyric acid (GABA)-mediated transmission in rat brain and induces anxiety and panic attacks in humans, elicited a proconflict effect. Exposure of rats for 1 min to CO2 decreased by approximately 40% the number of licking periods in the test. This effect was abolished by prior administration of alprazolam (0.5 mg per kilogram of body mass, i.p.). Although these results may support a role for GABA-mediated transmission in the anxiogenic effect of CO2 inhalation, the possibility that different neurotransmitters other than GABA are involved in the action of CO2 can not be ruled out.

Long-term treatment with abecarnil fails to induce tolerance in mice.

The effects of long-term treatment (3 times a day for 4 weeks) with a pharmacologically active dose (0.1 mg/kg i.p.) of the novel anxiolytic, abecarnil, on exploratory behaviour and [35S]TBPS (t-butylbicyclophosphorothionate) binding were compared to those of diazepam (1 mg/kg i.p.) in mice. A challenge dose (0.1 mg/kg) of abecarnil given 12 h after the last administration of the treatment protocol markedly inhibited exploratory behaviour in animals treated chronically with abecarnil (-62%) or vehicle (-87%). Consistent with this behavioural effect, the same challenge dose of abecarnil significantly reduced [35S]TBPS binding to unwashed cerebral cortical membranes from mice treated chronically with abecarnil (-28%) or vehicle (-30%). In contrast, a challenge dose (1 mg/kg) of diazepam failed to affect motor behaviour and [35S]TBPS binding in mice chronically exposed to diazepam; in animals chronically treated with vehicle, diazepam markedly inhibited both exploratory behaviour (-55%) and [35S]TBPS binding (-21%). These results indicate that long-term treatment with abecarnil failed to induce tolerance to the effect of this drug on gamma-aminobutyric acid type A (GABAA) receptor function. Accordingly, [35S]TBPS binding was increased (+15-26%) 12 and 48 h after discontinuation of long-term diazepam administration while no such increase in [35S]TBPS binding was observed for mice chronically treated with abecarnil. Moreover, whereas a significant decrease (-15%) in [35S]TBPS binding was observed 96 h after discontinuation of long-term diazepam treatment, chronic treatment with abecarnil did not modify this parameter. Together, these data indicate that long-term treatment with a pharmacologically effective dose of abecarnil did not induce tolerance or the discontinuation syndrome in mice.

Chronic administration of an anticonvulsant dose of imidazenil fails to induce tolerance of GABAA receptor function in mice.

The ability of an anticonvulsant dose (0.1 mg/kg i.p.) of imidazenil, a new partial agonist of benzodiazepine receptors, to antagonize the convulsions and the increase in t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to the gamma-aminobutyric acid type A (GABAA) receptor elicited by isoniazid, an inhibitor of central GABAergic function, was evaluated in mice chronically treated (3 times daily for 30 days) with the same dose of imidazenil. The challenge dose of imidazenil, administered 36 h after the last injection of the chronic treatment protocol, reduced both isoniazid-induced convulsions and the isoniazid-induced increase in [35S]TBPS binding to the same marked extent as in control mice. These results indicate that long-term treatment with a pharmacologically effective dose of imidazenil failed to induce tolerance to both the anticonvulsant effect and the positive modulatory action on GABAA receptor function of this drug in mouse brain.

Failure of dark adaptation to upregulate D-1 dopamine receptors in retina of senescent rats.

The effect of aging on the binding parameters of 3H-SCH 23390, the most selective ligand of D-1 DA receptors, was studied in membrane preparations from the rat retina. DA-stimulated adenylate cyclase activity was also measured in order to better characterize the changes in retinal D-1 DA receptors induced by aging. The binding studies revealed that the density of 3H-SCH 23390 was increased (34 and 73%) in the retina of 14- and 26-month-old rats, when compared to young adult animals, respectively. In contrast, aging failed to alter the sensitivity of the adenylate cyclase to the action of DA. In fact, DA (10(-6) M to 10(-4) M) elicited a similar enhancement in cyclic AMP formation in retinal homogenates of both adult and senescent rats. Since dark adaptation increases the density of D-1 DA receptors in the retina of adult rats we studied the effect of light deprivation on 3H-SCH 23390 binding and DA-sensitive adenylate cyclase activity in the retina of senescent rats. As previously shown (25) light deprivation increased 3H-SCH 23390 binding and enhanced DA-sensitive adenylate cyclase activity in the retina of young adult rats. On the contrary, dark adaptation failed to increase 3H-SCH 23390 binding and to enhance DA-sensitive adenylate cyclase activity in the retina of senescent rats. Taken together these results indicate that D-1 DA receptors in the retina of aged rats have biochemical and functional properties different from those found in the retina of adult animals; these changes may result in an altered response to the physiological stimuli elicited by environmental lighting.

Differential effect of aging on 3H-SCH 23390 binding sites in the retina and in distinct areas of the rat brain.

The effects of age on the binding parameters of the selective D-1 dopamine (DA) receptor antagonist 3H-SCH 23390 were studied in membrane preparations from rat striatum, substantia nigra, olfactory tubercle, prefrontal cortex and retina. When compared with 3-month-old animals, there was a significant decrease in the density of 3H-SCH 23390 binding sites in the striatum (-25%), substantia nigra (-24%), and olfactory tubercle (-23%), but not in the prefrontal cortex of senescent (23-month-old) rats. The affinity of 3H-SCH 23390 for D-1 DA receptors did not change with age in any of the brain areas analyzed. In contrast, the density of 3H-SCH 23390 binding sites was higher (+53%) in the retina of aged rats that in 3-month-old controls. Confirming previous studies, we observed that light deprivation induced a significant increment in the density of 3H-SCH 23390 binding sites in the retina of adult rats (+31%) but not in the retina of aged animals. The ability of light exposure to activate DAergic neurons in the rat retina was not altered by normal aging. In fact, a similar increase in the concentration of DOPAC was observed in the retina of light-adapted adult and senescent rats when compared to their respective dark-adapted controls (+94% and +95%, respectively). The results indicate that aging has a differential effect on D-1 DA receptors in the retina and different areas of the rat brain. Finally, the age-related increment in the density of retinal D-1 DA receptors does not appear to depend on presynaptic mechanisms, since DA metabolism is increased by light to the same extent in young and aged rats.

Involvement of D1 and D2 Dopamine Receptors in the Control of Horizontal Cell Electrical Coupling in the Turtle Retina.

We studied the actions of D1 and D2 dopamine agonists and antagonists on the coupling of horizontal cell axons in the turtle retina by a combination of pharmacological and electrophysiological methods. Both D1 and D2 receptors were identified in membrane fractions by radioligand binding using [3H]-SCH 23390 and [3H]-spiperone, respectively. The KD of both receptor classes were identical (0.21 nM) but D1 receptor density exceeded that of D2 receptors by more than four-fold. D1 agonists increased the activity of adenylate cyclase in a dose-dependent manner, whereas D2 agonists were without significant effect by themselves, nor did D2 antagonists block the D1-mediated increase in adenylate cyclase activity. Intracellular recordings and Lucifer Yellow dye injections were used to characterize the modifications of the receptive field profile of horizontal cell axons (H1AT) exposed to different pharmacological agents. Dopamine or D1 agonists (0.05 - 10 microM) induced a marked constriction of the H1AT receptive field, whereas D2 agonists elicited a small expansion of the receptive field. However, in the presence of a D1 antagonist, as well as IBMX to inhibit phosphodiesterase, D2 agonists (10 - 70 microM) induced a marked increase in the receptive field profile. These results indicate that both D1 and D2 dopamine receptors play a role in shaping the receptive field profile of the horizontal cell axon terminal in the turtle retina.

D1 dopamine receptors in the rat retina: effect of dark adaptation and chronic blockade by SCH 23390.

Chronic administration of SCH 23390 (0.03 mg/kg s.c., three times daily), a selective D1 dopamine (DA) receptor blocker, markedly increased the [3H]SCH 23390 binding in the rat retina. As revealed by the Scatchard plot analysis of saturation data from retinal homogenates, chronic SCH 23390 increased the total number of binding sites by 34% when compared to tissue from solvent-treated rats but failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. The up-regulation of [3H]SCH 23390 binding sites was paralleled by an increase in the sensitivity of retina DA-sensitive adenylate cyclase. In fact, DA (5 X 10(-6) M to 10(-4) M) produced a higher accumulation of cyclic AMP (from 58 to 128%) in the retina of SCH 23390-treated rats as compared to the accumulation (from 35 to 80%) found in tissue from solvent-treated rats. Since dark adaptation decreases dopaminergic function in the rat retina, the influence of environmental lighting on [3H]SCH 23390 binding and DA-sensitive adenylate cyclase activity was studied. After 4 h of dark adaptation the density of [3H]SCH 23390 binding sites was higher (32%) than that from light-adapted rats. On the other hand, dark adaptation failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. Moreover, DA elicited a greater stimulation of adenylate cyclase activity in homogenates of retina from dark-adapted rats. Thus, the maximum adenylate cyclase response to DA resulted higher in the retina of dark-adapted rats (152%) than that found in the retina of light-adapted animals (97%).(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental and age-related changes in D1-dopamine receptors and dopamine content in the rat striatum.

The relationship between the postnatal development of dopaminergic (DAergic) nerve endings and the maturation of D1 DA receptors in the rat striatum was analyzed by measuring the content of DA and dihydroxyphenylacetic acid (DOPAC), two biochemical markers of DAergic nerve terminal proliferation, and the ontogenetic changes in [3H]SCH 23390 binding sites. DA-stimulated adenylate cyclase (AC) activity was also measured in order to characterize the coupling of [3H]SCH 23390 binding sites to the responses mediated by the activation of D1 DA receptors. Striatal levels of DA and DOPAC, as well as the density and affinity of [3H]SCH 23390 binding sites and DA-stimulated AC activity were also measured in senescent rats. The striatal content of DA increased slowly after birth, reaching adult levels by postnatal day 60 and remaining constant through adulthood and senescence (up to 20 months of age). The density of [3H]SCH 23390 binding sites increased 14-fold from birth to postnatal day 35, when a peak value was reached, whereas a significant decrease was observed in the striatum of aged rats. In contrast, the affinity of D1 DA receptors for [3H]SCH 23390 remained unchanged from birth through senescence. The stimulation of cyclic AMP formation induced by 100 microM DA increased 4-fold from birth to postnatal day 14, when the maximal responsiveness to DA was observed and then returned to adult levels. No significant alterations were observed in the Km values during development, whereas the stimulatory effect of 100 microM DA on AC activity was significantly decreased in senescent rats.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Hydroxydopamine-induced degeneration of nigral dopamine neurons: differential effect on nigral and striatal D-1 dopamine receptors.

Dopamine-sensitive adenylate cyclase and 3H-SCH 23390 binding parameters were measured in the rat substantia nigra and striatum 15 days after the injection of 6-hydroxydopamine into the medial forebrain bundle. The activity of nigral dopamine-sensitive adenylate cyclase and the binding of 3H-SCH 23390 to rat nigral D-1 dopamine receptors were markedly decreased after the lesion. On the contrary, 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway enhanced both adenylate cyclase activity and the density of 3H-SCH 23390 binding sites in striatal membrane preparations. The changes in 3H-SCH 23390 binding found in both nigral and striatal membrane preparations were associated with changes in the total number of binding sites with no modifications in their apparent affinity. The results indicate that: within the substantia nigra a fraction (30%) of D-1 dopamine receptors coupled to the adenylate cyclase is located on cell bodies and/or dendrites of dopaminergic neurons; striatal D-1 dopamine receptors are tonically innervated by nigrostriatal afferent fibers.