Biomedical subjects

D Duterte-Boucher

Publications and source records attributed to D Duterte-Boucher.

16 recordsLinked to original sources

PubMed2003

Differential effects of novelty exposure on place preference conditioning to amphetamine and its oral consumption.

RATIONALE: Sensation/novelty seeking is frequently observed in drug abusers. Rats with high locomotor activity in response to inescapable novelty may be more prone to drug addiction. However, it is not clear whether this response to novelty represents reactivity to the novelty-induced stress or seeking for novelty. OBJECTIVES: We have compared the influence of the response to novelty-presented in a forced stressful or in a free choice non-stressful manner-on vulnerability to addictive properties of amphetamine. METHODS: Wistar rats were selected according to their (i) reactivity to inescapable novelty and (ii) novelty preference. For this purpose, animals were exposed during two 30-min sessions, 24 h apart, to the same compartment; their motor activity during the first session was used as an index of reactivity. On the third day, they were allowed to choose between this "familiar" environment and a novel one. Rewarding properties of amphetamine (0.2-3.2 mg/kg, s.c.) were determined by place conditioning. Amphetamine oral consumption (10-50 mg/l) in a free-choice paradigm was measured over a period of 32 days. RESULTS: Reactivity to novelty and novelty preference were not correlated. Reactivity to inescapable novelty predicted place conditioning induced by the lowest dose of amphetamine, whereas preference for novelty did not. High responders to inescapable novelty consumed less amphetamine than low responders. Novelty preference was positively correlated to amphetamine oral consumption only at the lowest concentration. CONCLUSIONS: Reactivity to inescapable novelty and novelty preference represent different behavioural components, which are related differentially with amphetamine place conditioning and its oral consumption.

Administration, Oral↗

PubMed1998

Pre-exposure to alcohol does not sensitize to the rewarding effects of cocaine.

The conditioned place preference (CPP) induced by cocaine 2.5 mg/kg was measured in rats pre-exposed to ethanol (14 days with only 10% v/v ethanol followed by a free choice between ethanol solution and water for 14 days). Rats were divided according to their alcohol intake during the free choice period into low-drinking (<3 g/kg per day), intermediate-drinking and high-drinking (> 4 g/kg per day) rats. Cocaine-induced CPP was not modified in high-drinking rats relative to controls. Low-drinking rats had a lower CPP than high-drinking rats and controls. We conclude that pre-exposure to alcohol did not sensitize to the cocaine rewarding effects, and that alcohol low-drinking rats showed the lowest preference for cocaine.

Alcohol Drinking↗

PubMed1998

Sensitization to the rewarding effects of the specific dopamine uptake inhibitor GBR12783.

The conditioned place preference (CPP) induced by increasing doses (1.25-40 mg/kg) of cocaine or the specific dopamine uptake inhibitor GBR12783 was investigated in rats previously treated with cocaine (10 or 20 mg/kg), GBR12783 (10 mg/kg) or morphine (10 mg/kg) for 15 days. In solvent-pretreated rats, cocaine- and GBR12783-induced CPPs were biphasic, with the highest scores observed at 20 mg/kg. Prior exposure to GBR12783 sensitized the rats to the rewarding effects of low doses of either GBR12783 or cocaine. Pretreatment with cocaine 20 mg/kg, but not 10 mg/kg, sensitized the rats to its own rewarding effects. Furthermore, it was less efficient than GBR12783 in sensitizing the animals to the rewarding effects of both drugs. These data confirm the major role of dopamine uptake inhibition in the sensitization process. On the other hand, the magnitude of CPP induced by a high dose of both drugs (20 mg/kg) was decreased after pretreatment with either GBR12783 or cocaine, reaching the lower scores observed at 40 mg/kg. This decrease was unrelated to altered anxiety level but was associated with sensitization to stereotypies. Morphine pretreatment modified neither the CPP induced by high doses of cocaine or GBR12783 nor cocaine- or GBR12783-induced stereotypies. However, prior exposure to morphine sensitized the rats to the rewarding effects of cocaine (2.5 mg/kg) but not to those of GBR12783, suggesting that other mechanisms working in concert with dopamine may facilitate the rewarding effect of cocaine without affecting that of GBR12783.

Animals↗

PubMed1996

Place conditioning with cocaine and the dopamine uptake inhibitor GBR12783.

The rewarding and locomotor effects of the specific dopamine uptake inhibitor GBR12783 (2.5-20 mg kg-1, i.p.) were compared with those of cocaine. For both drugs, all doses produced a conditioned place preference (CPP), even the dose of 2.5 mg kg-1, which did not modify the locomotor activity. Despite an equivalent locomotor stimulation, the magnitude of CPP induced by cocaine (10 mg kg-1) was greater than that induced by the same dose of GBR12783. This confirms the involvement of dopamine uptake inhibition in reward, but underlines differences in relative efficacies in rewarding and motor effects of both drugs and suggests that these two properties are, at least in part, separable anatomically or functionally.

Animals↗

PubMed1996

Locomotor sensitization to [D-Trp(11)]neurotensin after repeated injections of the dopamine uptake inhibitor GBR12783 in rats.

Rats received one daily i.p. injection of the dopamine uptake inhibitor GBR12783 (1-[2-(diphenylmethoxy)ethyl]4-(3-phenyl-2-(propenyl)-piperazine) (10mg/kg) or vehicle for 9 days. Fourteen days after discontinuing treatment, their locomotor activity was assessed after injection of GBR12783 (5 mg/kg) or vehicle, then 6 days later, after i.c.v. injection of [D-Trp(11)]neurotensin (750 ng) or saline. A sensitization to the stimulant locomotor effects of both GBR12783 and [D-Trp(11)]neurotensin occurred in rats exposed to the actimeter following the 1st, 5th and 9th injections of GBR12783. Rats without prior experience of the activity cages before the challenge tests showed no sensitization to either GBR12783 or [D-Trp(11)] neurotensin. Our data suggest that a similar mechanism may underlie the locomotor sensitization to GBR12783 and the heterosensitization to [D-Trp(11)]neurotensin.

Animals↗

PubMed1996

Locomotor sensitization and decrease in [3H]mazindol binding to the dopamine transporter in the nucleus accumbens are delayed after chronic treatments by GBR12783 or cocaine.

Rats were treated once daily for 15 consecutive days with either cocaine or the specific dopamine uptake inhibitor 1-[2- (diphenylmethoxy)ethyl]-4-(3-phenyl-2-(propenyl)-piperazine (GBR12783) at a dose (10 mg/kg) that given acutely increases locomotor activity. Two or 14 days after the last administration, the motor stimulant responses of rats to a challenge dose (5 mg/kg) of the drug administered previously were compared with the motor stimulant responses of rats daily injected with solvent. A sensitization to the acute stimulant locomotor effect of these drugs was only observed 14 days after cessation of chronic treatments. After this withdrawal period, autoradiographic analysis revealed a significant decrease in the desipramine-insensitive [3H]mazindol binding to the dopamine transporter in the shell of the nucleus accumbens. No change was noticed in other regions with high dopamine content: core of nucleus accumbens, striatum, olfactory tubercle, substantia nigra and ventral tegmental area. Absence of concomitant decrease in [3H]dihydrotetrabenazine labeling, which indicates lack of effect on vesicular monoamine transporters, suggests that the decrease in accumbal [3H]mazindol binding did not result from a cytotoxic effect on corresponding dopamine neurons. In addition, 14 days after the last administration of GBR12783, the levels of dopamine and metabolites (dihydroxy-phenylacetic acid, homovanillic acid) and the ability of acute GBR12783 to synergize with haloperidol-induced increase in these metabolites were not modified either in the whole nucleus accumbens or in the striatum.

Animals↗

PubMed1994

Invariance of the density of dopamine uptake sites and dopamine metabolism in the rat brain after a chronic treatment with the dopamine uptake inhibitor GBR 12783.

A chronic treatment (10 mg/kg, twice daily during 9 days) with the dopamine uptake inhibitor GBR 12783 was performed in rats at a dose increasing their locomotor activity. Forty-eight hours after the last administration, animals were sacrificed and 3H mazindol binding was performed on brain slices. Autoradiographic analysis revealed no change in this binding relatively to control animals in regions with high dopamine contents: striatum, nucleus accumbens, olfactory tubercle, substantia nigra and ventral tegmentum area. The treatment did not either modify the levels of dopamine (DA) and metabolites (HVA, DOPAC) both in the striatum and the nucleus accumbens. Thus, early after the end of the treatment, the chronic blockade of the dopamine uptake complex regulates neither the dopamine uptake complex nor the dopamine metabolism.

Afferent Pathways↗

PubMed1993

In vivo occupancy of the striatal dopamine uptake complex by various inhibitors does not predict their effects on locomotion.

We compared the ability of various dopamine (DA) uptake inhibitors to displace the in vivo striatal [3H]GBR 12783 (1-[2(diphenylmethoxy) ethyl)-4-(3-phenyl-1[3H]-2-propenyl)-piperazine) binding with their stimulant effect on locomotor activity on mice. GBR 12783 (8 mg/kg), GBR 13069 (10 mg/kg), cocaine (20 mg/kg), mazindol (3 mg/kg) or pyrovalerone (2 mg/kg) stimulated locomotion as long as they occupied the DA uptake complex. In contrast, nomifensine (3 mg/kg) did not stimulate locomotion although it competed with [3H]GBR 12783 for the occupancy of the DA uptake complex at a significant level (> 50%). Administered at their ED50 doses, GBR 12783, BTCP (N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine, GBR 13069, amineptine and dexamphetamine significantly increased locomotor activity whereas the other inhibitors tested did not. The locomotor response elicited by GBR 12783 (10 mg/kg) was not decreased by desipramine (20 mg/kg) nor by oxaprotiline (10 mg/kg). The increase in locomotion elicited by GBR 12783 was positively correlated with the basal locomotor activity of the mice. The stimulant effect of GBR 12783 was potentiated by SKF 525A and by budipine. Additional pharmacological properties might conceal the relationship between the effects of some DA uptake inhibitors on locomotion, and on in vivo occupancy of DA uptake sites.

Animals↗

PubMed1992

Dopaminergic transmission and (+)amphetamine-induced lethality in aggregated mice.

In aggregated mice the lethal dose 50% (LD50) of (+)amphetamine was found to be clearly lower than in isolated animals (dose ratio: 6:1), whereas with the pure dopamine uptake inhibitor GBR 12783, the ratio was only 2. Pretreatment of mice with GBR 12783 (20 or 40 mg/kg ip) did not reduce the lethality of (+)amphetamine (10 mg/kg) in aggregated mice. Taking into account their relative affinity for D1 and D2 dopamine receptors, various DA antagonists were opposed to (+)amphetamine (20 mg/kg) in aggregated mice. The specific D1 antagonist SCH 23390 was especially effective (ID50 10 micrograms/kg). The specific D2 antagonists (+/-) sulpiride and metoclopramide were effective for high doses (ID50 = 43 and 19 mg/kg respectively). The dopamine antagonists haloperidol and alpha-flupenthixol, less specific as regards D1 vs D2 receptors, had an ID50 of 66 and 186 micrograms/kg respectively. Association of the D1 antagonist SCH 23390 with the D2 antagonist (+/-) sulpiride resulted in an apparent additive effect for reducing the (+)amphetamine-induced lethality. A semi-chronic treatment with either the D1 agonist SKF 38393 (7 x 20 mg/kg) or (+)amphetamine (6 x 10 mg/kg) performed in isolated mice did not reduce the lethality induced by (+)amphetamine (20 mg/kg) in aggregated mice. The antagonism of the (+)amphetamine-induced lethality in aggregated mice, frequently used to screen meuroleptics, reveals their antagonistic activity towards D1 or D2 dopamine receptor types.

Amphetamine↗

PubMed1991

Stimulation of D1 and D2 dopamine receptors produces additive anorectic effects.

In food-deprived mice the D1 dopamine agonist SKF 38393 induced dose dependent anorexia (ED50 = 2.6 mg/kg). This effect was reversed by the D1 antagonist SCH 23390. In similar conditions, the D2 dopamine agonist RU 24926 also induced dose dependent anorexia (ED50 = 0.19 mg/kg). This effect was reversed by the D2 antagonist (+/-) sulpiride. The mixed D1/D2 agonist apomorphine also induced an anorectic effect (150 micrograms/kg sc) which was completely reversed by (+/-) sulpiride (25 mg/kg, ip) but unaffected by SCH 23390 (5-30 micrograms/kg). The dose response curve obtained by associating SKF 38393 (2.5 mg/kg) with increasing doses of RU 24926 was roughly parallel to that obtained with RU 24926 alone. This indicates that effects of two drugs were additive. Although both D1 and D2 receptors regulate food consumption, the anorectic effect of apomorphine appears to involve only D2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1990

Comparison of the effects of three indirect dopamine agonists, GK 13, GBR 12783 and dexamphetamine on behavioural tests involving central catecholaminergic transmissions.

GK 13 (N-[1-(2-benzo (b) thiophenyl)-cyclohexyl] piperidine), GBR 12783 (1-[2-(diphenylmethoxy)-ethyl] 4-(3-phenyl propenyl)-piperazine and dexamphetamine are three indirect catecholaminergic agonists, acting via different neurochemical mechanisms. We have compared their effects in rodents, in several behavioral tests. All three drugs increased locomotion. The stimulant locomotor effect of dexamphetamine was more easily antagonized by haloperidol than that of GBR 12783 and GK 13. Only dexamphetamine reversed reserpine-induced akinesia. This reversal was prevented by pretreatment with either GK 13 or GBR 12783. The three drugs reduced pentobarbital sleeping time in mice. They induced rotation ipsilateral to a unilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. The stereotypies induced by GK 13 and GBR 12783 were essentially limited to sniffing. Haloperidol-induced catalepsy was apparently more easily antagonized by dexamphetamine than by GK 13 or GBR 12783. GK 13 and GBR 12783 had no significant effects on body temperature. The three drugs displayed an anti-immobility effect in the "despair test". Dexamphetamine and GK 13 reversed the hypothermia induced by apomorphine (16 mg/kg), as well as reserpine-induced hypothermia and reserpine-induced ptosis. Dexamphetamine induced a dose-dependent anorectic effect, whereas GK 13 and GBR 12783 induced only a brief and partial anorexia. Similar observations were made on water intake. Pretreatment with either GBR 12783 or GK 13 did not affect the dexamphetamine-induced anorexia. Effects of the three drugs are discussed by reference to their known neurochemical properties on catecholaminergic transmission.

Animals↗

PubMed1990

Dopamine D1 and D2 receptors mediate opposite effects of apomorphine on the body temperature of reserpinized mice.

In mice, rendered poikilothermic by a prior (18 hr) subcutaneous administration of reserpine (3 mg/kg), the subcutaneous administration of apomorphine increased dose-dependently the body temperature. This effect was potentiated by the specific D2 dopamine antagonist sulpiride. On the contrary, it was reduced by the specific D1 dopamine antagonist SCH 23390. A desensitization of D2 receptors was produced by the repeated administration of the specific D2 agonist RU 24926. This pretreatment led to an increased efficacy of apomorphine in antagonizing reserpine-induced hypothermia. Similarly, a desensitization of D1 receptors was created by the repeated administration of the specific D1 agonist CY 208-243. This pretreatment significantly diminished the efficacy of apomorphine in antagonizing reserpine-induced hypothermia. The repeated administration of the D1 agonist CY 208-243, in non-reserpinized mice, significantly increased the hypothermic effect of apomorphine (1 mg/kg). Thus, it appears that, in normal mice, but especially in reserpinized mice, the stimulation of D1 receptors by apomorphine induces an increase in body temperature that is masked, especially in normal mice, by the hypothermic effect, resulting from the simultaneous stimulation of D2 receptors.

Animals↗

PubMed1989

Appearance of a stereotyped apomorphine-induced climbing in unresponsive DBA2 mice after subchronic manipulations of brain dopamine transmission.

DBA2 mice show an erratic spontaneous climbing which is reduced by increasing doses of direct dopamine agonists (apomorphine up to 5 mg/kg, piribedil up to 20 mg/kg). Sustained stereotyped climbing occurs when animals are treated with L-dopa plus benserazide and dexamphetamine. In this strain, which is spontaneously insensitive to apomorphine-induced climbing, this behaviour progressively appeared in a stereotyped manner after repeated administrations of apomorphine (5 mg/kg). The sensitization to apomorphine-induced climbing is long-lasting (more than 15 days). A similar sensitization may be induced by repeated administrations of either piribedil or of the dopamine uptake inhibitor GBR 12783. The semichronic reduction in dopaminergic transmission induced by four administrations of haloperidol (2 mg/kg at 2-day intervals) or by pretreatment with reserpine (3 mg/kg) induced sensitization to apomorphine-induced climbing. These results are discussed in terms of modifications in the sensitivity of two types of dopamine receptors exerting opposite effects on climbing behaviour.

Animals↗

PubMed1989

Stimulation of central D1 dopamine receptors reverses reserpine-induced hypothermia in mice.

In mice rendered poikilothermic by a prior (18 h) subcutaneous administration of reserpine (3 mg/kg) the injection of the D1 dopamine agonist SKF 38393 in doses of 1 mg/kg or more increased dose-dependently, the body temperature. The D1 dopamine antagonist SCH 23390, administered subcutaneously, antagonized, with an ID50 of 16 micrograms/kg, the reversal by SKF 38393 of reserpine-induced hypothermia. The intracerebroventricular administration of 1 microgram per mouse of SKF 38393 was sufficient to elevate by about 7 degrees C the temperature of reserpinized mice. It is concluded that stimulation of central D1 dopamine receptors leads to a marked reversal of reserpine-induced hypothermia; this may constitute a new test to investigate interaction of drugs with these receptors. In reserpine-pretreated mice, the dopamine (DA) agonist apomorphine, which stimulates both the D1 and D2 subtypes of DA receptors, increases body temperature according to a mechanism insensitive to the specific D2 DA antagonist sulpiride (Horowski 1978) or the preferential D2 DA antagonist haloperidol (Danielson, Coutts, Keashly and Tang 1985). This observation led us to believe that D1 DA receptors could be involved in the reversal of the hypothermia induced by reserpine. To check more directly the involvement of D1 DA receptors in the reversal of the reserpine-induced hypothermia we have tested the specific D1 agonist SKF 38393 (Setler, Sarau, Zirckle and Saunders, 1978), administered peripherally or intracerebroventricularly and we have studied its interaction with the specific D1 antagonist SCH 23390 (Iorio, Barnett, Leitz, Houser and Korduba, 1983).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Characteristics of the dopamine receptors involved in the anorectic effects of apomorphine in mice.

In food-deprived mice apomorphine injected SC induced a brief (15-30 min) dose-dependent (30-150 micrograms/kg) reduction in food intake. This effect occurred in naive mice as well as in mice habituated to a food deprivation procedure. The anorectic effect of apomorphine (150 micrograms/kg SC) was antagonized by sulpiride (ID50 = 8.6 mg/kg) and by haloperidol (ID50 = 66 micrograms/kg) but domperidone was ineffective (250 micrograms/kg). Mice submitted to a semi-chronic (6 d) blockade of dopamine receptors by haloperidol or injected intracerebroventricularly with 125 micrograms 6-hydroxydopamine 21 d before testing failed to develop a hypersensitivity to the anorectic effect of apomorphine (60 micrograms/kg). Although a single apomorphine injection (5 mg/kg) induced tolerance to the hypothermic effect of a second apomorphine injection of 150 micrograms/kg, it did not modify the anorectic effect. Repeated apomorphine injection (5 x 5 mg/kg) resulted in a slight but significant reduction in apomorphine-induced anorexia. A similarly significant reduction was not observed in mice submitted to repeated injections of dexamphetamine (5 x 5 mg/kg).

Animals↗

PubMed1988

Acute effects of direct dopamine agonists in the mouse behavioral despair test.

All the dopamine agonists (apomorphine, dipropylamino-5,6-dihydroxytetrahydronaphtalene, piribedil, bromocriptine, CBM 36-733) tested in the 'behavioral despair' test performed in mice had a dose-dependent anti-immobility effect, with the exception of the D-1 dopamine agonist, SKF 38393. This effect occurred at doses that reduced locomotor activity and decreased colonic temperature. A profound hypothermia of the same amplitude resulted from the immersion in water of the control and apomorphine (Apo)-treated mice. The anti-immobility effect of dopamine agonists depends on the stimulation of central dopamine receptors; this effect was antagonized more easily by haloperidol than by domperidone, and dipropylamino-5,6-dihydroxytetrahydronaphtalene was more effective than amino-5,6-dihydroxytetrahydronaphtalene. Their high sensitivity to sulpiride make it likely that the receptors involved correspond to the D-4 subtype. Blockade of dopamine receptors by haloperidol for about 5 days induced a slight hypersensitivity to the Apo effects. In contrast, tolerance to Apo occurred after administration of Apo, 5 mg/kg s.c., 24 and 16 h before testing. These data might reflect the potential antidepressant activity of direct dopamine agonists.

Animals↗