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M Cador

Publications and source records attributed to M Cador.

At least 19 recordsLinked to original sources
PubMed2004

Differential effects of dopaminergic agents on locomotor sensitisation and on the reinstatement of cocaine-seeking and food-seeking behaviour.

RATIONALE: The dopaminergic pathways are involved in natural and drug reward related processes. OBJECTIVES: To compare the respective involvement of the dopaminergic receptors D1, D2 and D3 in natural-seeking versus drug-seeking behaviour and evaluate any concomitant expression of locomotor sensitisation. METHODS: In separate experiments, male Wistar rats were trained to self-administer cocaine (0.25 mg/infusion) or to press a lever to obtain food pellets. Following a prolonged period of extinction, reinstatement of lever responding was measured following non-contingent food delivery, cocaine (15 mg/kg), D1-like (SKF 82958, 0.25 mg/kg), D2-like (quinelorane, 0.25 mg/kg) and D3-like (7-OHDPAT, 0.25 mg/kg) agonists. To demonstrate parallel expression of behavioural sensitisation, locomotor activity was recorded during the reinstatement sessions. RESULTS: Cocaine and quinelorane administrations reinstated cocaine-seeking behaviour and induced the expression of locomotor sensitisation, whereas SKF 82958 and 7-OHDPAT had either no effect or non-specific effects. In the food-seeking experiment, we found that quinelorane and 7-OHDPAT did not reinstate lever pressing. Cocaine increased responding on both active and inactive levers, whereas SKF 82958 had a more specific effect with higher responding on the previously food-associated lever. CONCLUSIONS: Our results indicate that expression of locomotor sensitisation and reinstatement of cocaine-seeking but not food-seeking behaviours are in part supported by common dopaminergic substrates, among which the D2 receptors play a crucial role.

Animals↗
PubMed2002

D-amphetamine-induced behavioral sensitization: effect of lesioning dopaminergic terminals in the medial prefrontal cortex, the amygdala and the entorhinal cortex.

The behavioral sensitization produced by the repeated administration of D-amphetamine is known to involve dopaminergic neurons in the mesoaccumbens pathway. Induction of this process is dependent on action of the drug in the ventral tegmental area while its expression involves action in the nucleus accumbens. We studied here the putative involvement of dopaminergic projections other than the mesoaccumbens in this phenomenon. We examined the influence of dopaminergic lesion of the medial prefrontal cortex, the amygdala and the entorhinal cortex in the behavioral sensitization produced by repeated injections of amphetamine either peripherally or directly into the ventral tegmental area of the brain. The repeated administration of amphetamine induced a behavioral sensitization, with the ventral tegmental area a critical site for induction of the process. This sensitization to amphetamine cross-reacted with morphine and was still observed 2 weeks after cessation of the treatment. Bilateral 6-hydroxydopamine lesion of dopaminergic terminals in either the medial prefrontal cortex or the amygdala, but not in the entorhinal cortex, prevented the development of behavioral sensitization to amphetamine and the cross-sensitization with morphine, whether the amphetamine pretreatment was administered peripherally or directly into the ventral tegmental area. In conclusion, these results indicated that behavioral sensitization to amphetamine, which involves dopaminergic neurons of the ventral tegmental area, is also dependent on dopaminergic neurotransmission of the medial prefrontal cortex and amygdala but not of the entorhinal cortex.

Amygdala↗
PubMed2002

Interaction between neuropeptide FF and opioids in the ventral tegmental area in the behavioral response to novelty.

Considerable evidence has focused on the interaction between endogenous opioid peptides and the dopaminergic mesocorticolimbic system in behavioral responses to stress. Recently, it has been proposed that the CNS synthesizes and secretes neuropeptides that act as part of a homeostatic system to attenuate the effects of morphine or endogenous opioid peptides. Among these antiopioids, neuropeptide FF (NPFF) is particularly interesting since both NPFF immunoreactive-like terminals and NPFF binding sites are located in the vicinity of the dopaminergic cell bodies within the ventral tegmental area (VTA) suggesting an interaction at this level. The purpose of the present study was to evaluate the respective implication of opioid and antiopioid peptides at the level of the VTA in the locomotor response to novelty in rats. The results indicate that s.c. naloxone pretreatment, an opiate receptor antagonist, reduced locomotor activity in rats placed in a novel environment without having any effect in a familiar environment. This effect takes place in the VTA since intra-VTA administration of naloxone methobromide diminished similarly and dose-dependently the motor response to novelty. This effect is mainly dependent on opioid peptides released at VTA level since local injections of thiorphan, an inhibitor of enkephalin degradation, strongly increased locomotor response to novelty and this effect is completely prevented by the co-administration of naloxone methobromide. When injected in the VTA, NPFF is acting as an antiopioid compound, i.e. it reduces the locomotor activity triggered by exposure to novelty to the level recorded in a familiar environment. Moreover, NPFF decreased dose-dependently the potentiation of novelty-induced locomotor response produced by VTA injection of thiorphan. Taken together, these results suggest that NPFF neurons may participate at the level of the VTA to a homeostatic regulating process counteracting opioid effects induced by a mild stress such as novelty.

Analgesics, Opioid↗
PubMed2000

Nicotine-induced locomotor activity is increased by preexposure of rats to prenatal stress.

Genetic factors are believed to play a predominant role in the individual differences observed in behavioral and pharmacological responses to drugs of abuse. An increasing literature indicates, however, that epigenetic factors can be involved as well. In this report we examined whether developmental changes induced by prenatal stress could alter the way animals respond to the psychostimulant effect of nicotine when adults. The results show that nicotine induces a dose-dependent increase of locomotor activity in both groups, and that prenatally-stressed animals exhibit a higher behavioral response at all doses. This study emphasizes the importance of early environment in the later development of drug-related behavior.

Animals↗
PubMed1999

D-amphetamine-induced behavioral sensitization: implication of a glutamatergic medial prefrontal cortex-ventral tegmental area innervation.

Behavioral sensitization to amphetamine is expressed as a progressive enhancement of the behavioral activating effects of the drug when repeated injections are performed as well as a long-lasting hypersensitivity to later environmental or pharmacological challenges. The mesoaccumbens dopamine system has been proposed to be the major candidate so far responsible for the induction and expression of this process, which are dependent on the action of amphetamine in the ventral tegmental area and nucleus accumbens, respectively. The development of this process has been proposed to be the result of an interaction between somatodendritically released dopamine and dopaminergic D1 receptors localized on different inputs to the ventral tegmental area, including glutamate afferents arising in part from mesocorticolimbic areas such as the medial prefrontal cortex and the amygdala. Three groups of experiments were designed to test the role of each of these components in the behavioral sensitization to amphetamine. First, the intervention of the glutamatergic transmission of the ventral tegmental area in the induction of sensitization to amphetamine was tested. The effects of an N-methyl-D-aspartate antagonist, 3-(R-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid. on the behavioral sensitization induced by amphetamine administered repeatedly in the ventral tegmental area was tested. It was found that the blockade of N-methyl-D-aspartate receptors with 3-(R-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid coadministered with amphetamine in the ventral tegmental area dose-dependently prevented the induction of sensitization. In a second step, the role of the structures which send glutamatergic inputs to the ventral tegmental area in the process of behavioral sensitization was tested. We evaluated the effects of ibotenic acid lesion of the medial prefrontal cortex and the amygdala on behavioral sensitization induced by peripheral or intra-ventral tegmental area administration of amphetamine. We found that ibotenic acid lesion of the medial prefrontal cortex blocked the behavioral sensitization induced by both intra-ventral tegmental area and peripheral treatment with amphetamine. In contrast, ibotenic acid lesion of the amygdala produced no effect on behavioral sensitization induced peripherally or centrally. These experiments confirmed (i) that the ventral tegmental area, where dopaminergic cell bodies are located, is a critical site for the induction of behavioral sensitization, (ii) that this process implicates the glutamatergic transmission in the ventral tegmental area, and (iii) that the medial prefrontal cortex is crucially implicated merely because of its direct glutamatergic inputs on to ventral tegmental area neurons. Together, these results reinforce the view that the behavioral sensitization to amphetamine implicates not only the mesoaccumbens dopaminergic neurons, but also other structures of the mesocorticolimbic system, such as the medial prefrontal cortex and more specifically its glutamatergic component.

Amygdala↗
PubMed1999

Total neurochemical lesion of noradrenergic neurons of the locus ceruleus does not alter either naloxone-precipitated or spontaneous opiate withdrawal nor does it influence ability of clonidine to reverse opiate withdrawal.

It has been suggested that an increase firing rate of noradrenergic neurons of the locus ceruleus is responsible for the opiate withdrawal syndrome. However, lesion studies have indicated that the noradrenergic neurons of the locus ceruleus are not essential for either the expression or suppression by clonidine of opiate withdrawal. The present study was designed to determine the effect of the almost complete 6-hydroxydopamine lesion of noradrenergic neurons (94%) of the locus ceruleus on various components of the opiate withdrawal syndrome and on its protection by clonidine. Morphine dependence was induced by s.c. implantation of morphine pellets (2 x 75 mg base). The following paradigms were used: 1) naloxone-induced conditioned place aversion, 2) naloxone-precipitated acute opiate withdrawal syndrome, 3) nycthemeral locomotor activity as a measure of spontaneous opiate withdrawal. The results showed that quasi-total lesion of noradrenergic neurons of the locus ceruleus did not modify opiate dependence as revealed by naloxone-induced conditioned place aversion and the expression of an acute morphine withdrawal syndrome. Moreover, clonidine prevented the opiate withdrawal syndrome in both lesioned and sham-operated rats, suggesting that the action of clonidine is certainly mediated through postsynaptic alpha(2)-adrenoceptor stimulation. Finally, the nycthemeral locomotor activity during spontaneous morphine withdrawal did not differ between the lesioned and the sham-operated rats.

Adrenergic alpha-Agonists↗
PubMed1998

Amphetamine-induced conditioned activity is insensitive to perturbations known to affect pavlovian conditioned responses in rats.

Psychostimulant-induced conditioned activity is characterized by the presence of a hyperactivity in drug-free rats exposed to an environment previously paired with the effects of a psychostimulant. This phenomenon is thought to result from a Pavlovian conditioning process. This hypothesis predicts that conditioned activity will be sensitive to perturbations known to affect classical conditioned responses. In direct contrast with this prediction, the authors report here that conditioned activity is insensitive to (a) the temporal order between the stimulant injection and the exposure to the environment, (b) unsignaled stimulant injections between drug-environment pairings, and (c) drug preexposures before the start of drug-environment pairings. It is concluded that the stimulant effects responsible for the establishment of conditioned activity may not be amenable to a Pavlovian associative process.

Amphetamine↗
PubMed1996

Evidence for selective involvement of dopamine D1 receptors of the ventral tegmental area in the behavioral sensitization induced by intra-ventral tegmental area injections of D-amphetamine.

The induction of behavioral sensitization to D-amphetamine (AMPH) is known to result at least in part from an action of the drug in the ventral tegmental area (VTA), which contains the dopamine (DA) A10 cell bodies. To specify the cellular mechanisms through which AMPH acts in the VTA and leads to behavioral sensitization after repeated intra-VTA injections, the involvement of VTA DA D1 and D2 and serotonin2 receptors in this phenomenon was investigated in independent experiments. The results reported here confirm that repeated intra-VTA AMPH injections (four injections of 5 micrograms/0.5 microliter every other day) induce behavioral sensitization, as revealed by the potentiation of the locomotor response to peripheral challenges with AMPH (0.5 mg/kg) 4 or 15 days after treatment. This behavioral sensitization induced by intra-VTA administration of AMPH cross-reacts with morphine (1 microgram/0.5 microliter) administered into the VTA 7 days after treatment. We demonstrated that the D1 receptor antagonist (R)-(+)-8-chloro-2,3,4, 5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (0, 0.01, 0.1 and 1 microgram/ 0.5 microliter) coadministered in the VTA with AMPH dose-dependently prevents the behavioral sensitization to peripheral AMPH challenges (at either 4 or 15 days after treatment) as well as the cross-sensitization with intra-VTA morphine. Neither DA D2 nor serotonin2 receptor blockade, using sulpiride (10 micrograms/0.5 microliters) and ketanserin (1 micrograms/0.5 microliters), respectively, had any effect on the induction of behavioral sensitization. In conclusion, these results demonstrate the selective involvement of VTA DA D1 receptors in the process by which AMPH acts in the VTA to induce behavioral sensitization.

Animals↗
PubMed1995

Prenatal stress in rats facilitates amphetamine-induced sensitization and induces long-lasting changes in dopamine receptors in the nucleus accumbens.

Exposure of rats to restraint stress during late pregnancy produces offspring with a variety of behavioral and neurobiological alterations. It has been suggested that prenatal stress leads to long-lasting changes in the hypothalamo-pituitary-adrenal axis in the offspring. One feature of prenatally-stressed rats is a susceptibility to amphetamine self-administration. Since this behavior has been related to amphetamine-induced sensitization and the activity of the mesolimbic dopamine system, we measured dopamine receptor densities and amphetamine-induced sensitization in these animals. The motor response to the first administration of amphetamine was similar in both prestressed and unstressed groups of adult animals, but after repeated drug injections, behavioral sensitization was observed sooner in the prenatally-stressed rats than in the controls. In separate groups of adult animals, densities of D1, D2 and D3 dopamine receptor subtypes in the striatum and nucleus accumbens were measured in prenatally-stressed and control rats by quantitative autoradiography using [3H]SCH23390, [3H]sulpiride and [3H]7-OH-DPAT as ligands respectively. Prenatal stress was found to produce the following alterations in the adult offspring: (i) no significant change in D1 receptor binding in either striatum or nucleus accumbens; (ii) a significant (+24%) increase in D2 receptor binding in the nucleus accumbens; (iii) a significant decrease in D3 receptor binding in both the shell (-16%) and the core (-26%) of the nucleus accumbens. These observations indicate that prenatal stress induces long-lasting changes in the dopamine sensitivity of the nucleus accumbens and in the capacity to develop amphetamine-induced sensitization in adulthood. The possible relationship between an impaired control of corticosterone secretion in prenatally-stressed animals and long-term changes in the mesolimbic dopamine system is discussed.

Amphetamine↗
PubMed1995

Short and long-term changes in dopamine and serotonin receptor binding sites in amphetamine-sensitized rats: a quantitative autoradiographic study.

The biochemical changes in DA and 5HT systems were investigated in amphetamine (AMPH)-sensitized rats, 1 and 15 days after cessation of treatment (5 mg/kg AMPH, i.p., twice a day for 6 days). At both times, AMPH-treated rats exhibited behavioral sensitization, as revealed by an enhancement of the stereotypic response to a challenge dose of 2 mg/Kg, ip. AMPH. Basal dopamine (DA) and serotonin (5-HT) metabolism was not significantly modified in different brain areas of AMPH-sensitized rats. Quantitative autoradiographic analysis of DA and serotonin 5-HT receptor subtypes was performed in the following brain regions: medial prefrontal cortex, nucleus accumbens, striatum, substantia nigra, ventral tegmental area, dorsal and median raphe nuclei. A significant increase of [3H]SCH 23390 binding to D1 DA receptors was observed in the substantia nigra pars reticulata 1 day but not 15 days after the cessation of AMPH treatment, whereas [3H]8-OH-DPAT binding to 5-HT1A sites was found to be significantly enhanced in the dorsal raphe nucleus at both time points. No change in D2 DA nor in 5-HT1B or 5-HT2A receptors was found in any of the brain structures examined at either time point. The obtained results suggest that DA and 5-HT systems are differently and time-dependently involved in AMPH-induced behavioral sensitization.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Social deprivation enhances the vulnerability of male Wistar rats to stressor- and amphetamine-induced behavioral sensitization.

The aim of the present study was to assess the influence of experiential factors on the vulnerability of rats to develop amphetamine (AMPH)- and stressor-induced behavioral sensitization. Young male Wistar rats with previous social experience were isolated from their peers for 2 weeks. 1) The effect of this short-lasting social deprivation were: a) a reduced tendency to explore a fearful environment; b) a prolonged exploratory activity in response to a novel but little fearful environment; and c) a dose-dependent increase in the psychomotor stimulation induced by systemic AMPH injection. 2) After repeated AMPH injections (injection every other day for 10 days), isolated rats exhibited behavioral sensitization at lower doses (0.5 and 0.75 mg/kg) than those required for group-housed rats (1 mg/kg). 3) After being submitted to a repeated stressor (3, 7 or 14 footshock sessions, with 2 days between sessions), the isolated rats exhibited a greater increase in the behavioral responsivity to a subsequent AMPH challenge (1 mg/kg) than did the group-housed rats regardless of the number of stress sessions. In conclusion, these results suggest that experiential factors such as privation of contact with peers (social isolation) may make rats more vulnerable to the long-term repercussions of chronic environmental and pharmacological challenges.

Amphetamine↗
PubMed1995

Ethopharmacological analysis of naloxone-precipitated morphine withdrawal syndrome in rats: a newly-developed "etho-score".

The intensity of opiate withdrawal syndrome in rats is usually quantified on the basis of selected physical signs or global scores. However, the selection criteria of signs and scores have not been subjected to an ethological discussion, hence they appear to be somewhat arbitrary. The objectives of this study were thus: i) to analyse the rat's behaviour during the naloxone-precipitated morphine withdrawal syndrome, ii) to evaluate the validity of classic methods, and iii) to design a new "etho-score". Ten rats were implanted with morphine pellets (75 mg x 2, SC), all receiving different naloxone doses following a within-subject design (0, 0.01, 0.05, 0.1, 0.5, 1 mg/kg SC). Twenty unexperienced rats and 20 with placebo pellets were injected with either saline or naloxone. Behaviour was videotaped and later analysed by computer-based ethological techniques. The ethogram encompassed 16 patterns displayed by rats during morphine withdrawal. Frequency, duration and latency of each pattern was measured, and a cluster analysis allowed discerning the structure of behaviour. Several physical signs and the Gellert-Holtzman score were also evaluated. The data revealed that writhing responses linearly changed in a dose-related fashion, and mastication was also enhanced after naloxone. Wet-dog shakes and jumping changed following an U-shaped curve. Significant changes in weight loss were found to be dose-dependent, and highly correlated to diarrhea. Learning effects were found to reliably affect exploration, writhing responses and some physical signs. The Gellert-Holtzman score was gradually enhanced after naloxone, being affected by learning as well. Naloxone affected lying and self-care responses in placebo rats. To sum up, the data indicated that: i) classic signs are useful, although most of them are disrupted by high naloxone or affected by learning effects, ii) the Gellert-Holtzman score was validated in this study, and iii) mastication and weight loss are good indicators of naloxone-precipitated morphine withdrawal, representing the basis of an "etho-score" which is herein proposed.

Animals↗
PubMed1995

Evidence of a complete independence of the neurobiological substrates for the induction and expression of behavioral sensitization to amphetamine.

The repeated administration of amphetamine in rats produces behavioral sensitization which is characterized either by a progressive enhancement of the locomotor activity induced by the drug or by an enduring behavioral hypersensitivity to the drug after the cessation of the treatment. Some authors have suggested that the action of amphetamine at the level of the nucleus accumbens is responsible for the expression of behavioral sensitization, whereas the action of amphetamine at the level of the dopamine cell bodies in the ventral tegmental area induces some changes responsible for the initiation of the phenomenon. The present study fully tested this hypothesis. In two separate experiments, the effects of different doses of amphetamine repeatedly administered in the ventral tegmental area or in the nucleus accumbens were tested on the later behavioral reactivity to the administration of amphetamine in the nucleus accumbens. Independent groups of rats received five repeated administrations (one injection every other day) of different doses of amphetamine either in the ventral tegmental area (0, 1, 2.5, 5 micrograms/0.5 microliters per side) or in the nucleus accumbens (0, 1, 3, 10 micrograms/l microliters per side). Two days following the last intracerebral amphetamine injection, each group received a phosphate buffer solution challenge directly into the nucleus accumbens followed two days later by an amphetamine challenge (1 microgram/l microliters per side) in the nucleus accumbens and two days later by a peripheral challenge with amphetamine (0.5 mg/kg, s.c.). Locomotor responses were recorded following each injection. Results showed that injections of amphetamine into the nucleus accumbens induced a dose-dependent increase in locomotor activity which remained identical with the repetition of the injections. No difference between the different intra-accumbens pretreated groups was observed following the diverse phosphate-buffered saline solution and amphetamine challenges. In contrast, intra-ventral tegmental area administration of amphetamine did not produce any modification of locomotor activity. However, whereas no difference between the differently pretreated groups was observed following phosphate-buffered saline administration into the nucleus accumbens, a potentiation of the locomotor response to a challenge dose of amphetamine into the nucleus accumbens was observed which was dependent on the dose of amphetamine pretreatment into the ventral tegmental area. Similar potentiation was observed following peripheral challenge with amphetamine. Finally, cross-sensitization was observed when a challenge dose of cocaine (10 micrograms/1 microliter per side) was injected into the nucleus accumbens, as well as when a peripheral challenge dose of morphine (2.5 mg/kg, s.c.) was administered to the ventral tegmental area-pretreated groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Amphetamine↗
PubMed1995

Acute and chronic amphetamine treatments differently regulate neuropeptide messenger RNA levels and Fos immunoreactivity in rat striatal neurons.

Repeated administration of amphetamine results in the well known phenomenon of reverse tolerance or sensitization. However, little is known about cellular and molecular mechanisms underlying acute versus chronic response to amphetamine. In this paper, we investigated the effects of acute (1.5 or 5 mg/kg) and chronic (5 mg/kg/day for 14 days) amphetamine treatment on locomotor activity, stereotypy, Fos immunoreactivity and messenger RNA levels of molecules implicated in dopamine transmission in the rat striatum and substantia nigra. In agreement with other studies, acute amphetamine induced a dose dependent increase in locomotor activity and stereotypy. Also, a comparison between the behavior observed after the first injection and the last injection of amphetamine in chronically treated rats showed sensitization as demonstrated by a higher rating of stereotypy. We have found that acute and chronic amphetamine treatments differently modulate the activity of several output neurons. A double labeling procedure with Fos immunohistochemistry coupled with in situ hybridization demonstrated that acute amphetamine treatment induces Fos immunoreactivity predominantly in striatal neurons expressing substance P messenger RNA (77.07 +/- 1.42%). Only 32.6 +/- 2.07% of Fos immunoreactive neurons expressed preproenkephalin A messenger RNA. In chronic amphetamine treated rats, 56.21 +/- 1.32% of the Fos immunoreactive neurons expressed substance P messenger RNA while 52.12 +/- 1.84% expressed preproenkephalin A messenger RNA. Statistical analysis revealed that this difference is mainly due to a decrease in the density of substance P immunoreactive neurons in chronically treated rats in comparison to acute. Amphetamine treatments induced Fos immunoreactivity in the substantia nigra in non-dopamine neurons. As measured by quantitative in situ hybridization, acute amphetamine induced an increase in substance P, preproenkephalin A and dynorphin messenger RNA levels (+23 +/- 0.05%, +45 +/- 0.07% and +24 +/- 0.05%, respectively). No difference in these increases was observed in relation with the dose injected (1.5 or 5 mg/kg). Chronic amphetamine treatment enhanced only substance P and dynorphin messenger RNA levels (+23 +/- 0.04% and +42 +/- 0.04%, respectively). Neither acute nor chronic amphetamine treatment had any effects on D1 or D2 dopamine receptor messenger RNA levels. Our main conclusions are: (1) in acutely treated rats Fos is essentially expressed by substance P neurons; (2) in chronically treated rats, Fos immunoreactivity is expressed by the two efferent striatal populations (i.e. preproenkephalin A and substance P neurons) and the number of Fos immunoreactive neurons is reduced as compared with acute; (3) neuropeptide messenger RNA levels, but not dopamine receptor messenger RNAs, are affected in the response to acute or chronic treatment with amphetamine.

Amphetamine↗
PubMed1995

Amphetamine-induced conditioned activity in rats: comparison with novelty-induced activity and role of the basolateral amygdala.

A within-subject design was used to investigate the behavioral and neural basis of the conditioned activity induced by amphetamine in male Wistar rats. In this design, conditioned activity was inferred when the activity of a given rat following a vehicle injection was greater in its amphetamine-paired environment (CS+) than in its vehicle-paired environment (CS-). Conditioned activity (a) did not change in magnitude with the number of conditioning sessions, (b) did not differ from the level of activity recorded during the first exposure to the CS- (novelty), (c) had an extinction rate that was similar to the rate of habituation to the CS-, and (d) was not impaired by a bilateral excitotoxic lesion of the basolateral amygdala. Results are discussed in light of the incentive conditioning and habituation theories of conditioned activity.

Animals↗
PubMed1994

Cocaine sensitivity in Roman High and Low Avoidance rats is modulated by sex and gonadal hormone status.

Repeated exposure to stressful stimuli or psychostimulants increases sensitivity to the motoric effects of these drugs, i.e. behavioral sensitization. The objective of the present experiment was to determine the interaction between factors that modulate psychostimulant sensitivity, i.e. sex and circulating gonadal hormone levels, in rats with a genetically distinct locomotor response to novelty: Roman Low Avoidance rats (RLA) freeze while Roman High Avoidance rats (RHA) remain motorically active. Ninety-six male and female RHA and RLA rats were gonadectomized (GDX) just after weaning or as adults, or left gonadally intact. Each rat received a total of 9 injections of cocaine hydrochloride (10 mg/kg, IP), at 3-4 day intervals for 5 weeks. Locomotor activity was measured after each injection, and stereotypes were rated 1 x/week. Open field behavior (10 min) and plasma corticosterone were measured 2 weeks after the final injection. Overall, the RHA line was more sensitive to (1) cocaine's stereotypic effects, and (2) the influence of ovarian hormones on the cocaine's acute and sensitizing effects on locomotor activity. Therefore, genetic background not only determines cocaine sensitivity, but also the influence of gonadal hormones on locomotor activity. These interactions are relevant when considering the genetic contribution to abuse liability.

Animals↗
PubMed1994

Effects of morphine and naloxone on behaviour in the hot plate test: an ethopharmacological study in the rat.

The objectives of this study were: i) to analyse the effects of morphine and naloxone on the rat's behaviour in the hot plate test using an ethological approach, and ii) to compare the effectiveness of repeated versus single test paradigms. Animals received either morphine (0, 3, 6 or 9 mg/kg SC) or naloxone (0, 0.01, 0.1 or 1 mg/kg SC). For repeated hot plate measures, rats were tested before and 60, 120, 180 and 240 min following morphine treatment, as well as 30, 60, 90 and 120 min after naloxone injection. For the single test schedule, rats were tested only once 60 min after morphine or 30 min after naloxone administration, or at 60, 120, 180, 240 and 300 min after 9 mg/kg morphine treatment. Behaviour was videotaped and analysed by an ethogram and ethological techniques. A cluster analysis revealed that the most frequently displayed patterns could be categorised into exploratory sniffing reactions (walk-sniff, immobile-sniff) and noxious-evoked elements, including primary (paw-licking, stamping), escape (jumping, leaning posture) and independent (hindleg-withdrawal) patterns. During repeated tests, morphine treatment induced: i) a maximum hypoalgesic effect 60 min post-injection (noxious-evoked patterns were significantly reduced), and ii) an unexpected "thermal hyperreactivity rebound effect" after 120 min (paw-licking and hindleg-withdrawal were enhanced), although changes in hindpaw-licking are more indicative of a hyperalgesic rebound effect. Most changes were quite similar during the single test schedule at 60 and 120 min after morphine injection. With regard to naloxone treatment, jumping latency was significantly decreased during the repeated test schedule, but not on single exposure to the plate. Other elements were facilitated, however, in the single test (stamping, leaning posture, hindleg-withdrawal). The results indicated that both repeated and single tests paradigms are of value for testing the effects of morphine and naloxone on rats. However, under our conditions the single test paradigm gave a better picture of the overall effects of the drug. Learning as well as habituation and sensitization may mask certain effects during repeated tests. In conclusion, an ethological analysis of the rat's behaviour in the hot plate test following administration of morphine and naloxone has been validated in this study.

Animals↗