Biomedical subjects

C Spyraki

Publications and source records attributed to C Spyraki.

At least 37 records · Page 2Linked to original sources

PubMed1988

Cocaine-induced place conditioning: importance of route of administration and other procedural variables.

It has been shown that pretreatment with dopamine (DA) receptor blockers disrupts the effect of intravenously (IV) and intracerebrally (ICV), but not intraperitoneally (IP) administered cocaine on place preference conditioning (PPC). The present study was undertaken to further evaluate possible differences between IV and IP cocaine PPC. To this end, several factors which may differentially influence IV and IP cocaine PPC were examined. Firstly, dose-response effects were studied. Intravenous cocaine produced PPC within a narrow dose range (0.5-2.5 mg/kg). Animals receiving IV injections of 5 and 10 mg/kg cocaine experienced convulsions and did not show PPC. For IP cocaine a 10-fold increase in dose (10 mg/kg) and twice the number of training trials was required in order to obtain PPC equal in magnitude to that with IV cocaine (0.5 mg/kg; two trials). Cocaine PPC was retained at least 1 month. Following IV cocaine preference developed for the side associated with the drug regardless of whether the conditioning was to the least or most preferred side. After IP cocaine, preference developed for the drug side only when the drug was paired with the least preferred side. Rats trained with IV, but not IP, cocaine significantly preferred the drug familiar side to a novel compartment. Preference for the IV or IP cocaine side developed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation of the cocaine PPC. The results show PPC procedure to be a valid test for evaluating rewarding properties of IV cocaine. However, they fail to show rewarding effects of IP cocaine.

Animals↗

PubMed1988

A role for the mesolimbic dopamine system in the reinforcing properties of diazepam.

The conditioned place preference paradigm was used to investigate the neurochemical and neuroanatomical substrates which mediate the rewarding properties of diazepam. The results confirmed that diazepam (1 and 2.5 mg/kg, IP) produced place preference for a distinctive environment that had previously been paired with injections of the drug. Pretreatment with haloperidol (0.1 mg/kg) antagonised the place preference induced by diazepam (1 mg/kg). Pretreatment with domperidone (2 mg/kg) failed to influence this effect of diazepam. Haloperidol (0.1 mg/kg) and domperidone (2 mg/kg) alone did not produce place aversion. In separate experiments the diazepam-induced place preference was examined in rats having 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens. These animals did not show preference for the compartment associated with diazepam. Depletion of central noradrenaline produced by systemic injections of DSP4 did not affect diazepam-induced place preference conditioning. These findings suggest that dopamine-containing neurons of the mesolimbic system are a component of the neural circuitry that mediates the reinforcing properties of diazepam.

Animals↗

PubMed1988

Influence of oestrogen on spontaneous and diazepam-induced exploration of rats in an elevated plus maze.

An elevated plus-maze, used to identify anxiolytic effects of drugs (Pellow et al., 1985), reflected as increased open-arm exploration, was employed in cycling and ovariectomised rats, to determine the effect of diazepam on the cycle and, after ovariectomy, to investigate possible influences of treatment with oestradiol (10 or 100 micrograms/kg, s.c.) (acute: 1 day or subchronic: 3 days) to ovariectomised rats on the effect of diazepam (1 mg/kg, i.p.), studied 3, 24 and 72 hr after cessation of treatment. Cycling females, exhibiting 3 consecutive 4-day oestrous cycles and ovariectomised rats, 15 days after surgery, were used. There was a tendency for increased open-arm exploration by rats in proestrous and diestrous, as compared to the other phases of the cycle and to ovariectomised rats. Rats treated 24 hr after subchronic treatment with oestradiol also exhibited increased open-arm exploration. The anti-anxiety effect of diazepam was clearly shown in oestrous and metestrous but not in proestrous, diestrous or in ovariectomised rats. The effect of diazepam was abolished in rats tested 3 hr after acute small doses of estradiol and attenuated in rats tested 24 hr after subchronic administration of the hormone. The results suggest that oestradiol, administered in physiological doses, may have an inhibitory effect on the diazepam-induced anxiolysis.

Animals↗

PubMed1988

Behavioural and biochemical effects of haloperidol during the oestrous cycle of the rat.

The effects of two doses (1 and 2 mg/kg, i.p.) of haloperidol (HAL) on catalepsy, on concentrations of DA and DOPAC in frontal cortex, nucleus accumbens and striatum and on serum levels of oestradiol were investigated in intact female rats during the 4-day oestrous cycle. Catalepsy induced by haloperidol did not vary much during phases of the cycle. The turnover of DA in the cortex induced by haloperidol was significantly greater on proestrus and smaller on oestrus. The effect of haloperidol on the turnover of DA in the nucleus accumbens and in striatum was marginally affected by the oestrous cycle being greatest on oestrus. The levels of serum oestradiol were higher on proestrus and lower on oestrus. No significant differences were detected between diestrus and metestrus. After haloperidol there was a dramatic increase in serum oestradiol on oestrus, a slight increase on metestrus and diestrus and a decrease on proestrus. However, serum levels of oestradiol were not significantly different between phases of the cycle in rats treated with haloperidol. The results indicate that the oestrous cycle has a detectable influence on DAergic mechanisms in the frontal cortex and possibly in the tuberoinfudibular system, brought about by treatment with haloperidol.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Effects of ritanserin on the rewarding properties of d-amphetamine, morphine and diazepam revealed by conditioned place preference in rats.

The possibility that 5-HT2 receptors mediate the reinforcing properties of d-amphetamine, morphine and diazepam was investigated in rats, using ritanserin, a 5-HT2 antagonist, and the conditioned place preference paradigm. Ritanserin 1 or 2.5 mg/kg did not cause place conditioning. Place preference induced by 1.5 mg/kg d-amphetamine and 2 mg/kg morphine was inhibited and attenuated respectively by pretreatment with 2.5 mg/kg ritanserin. Diazepam- (1 mg/kg) induced place preference was completely blocked by both doses of ritanserin. Ritanserin pretreatment failed to influence amphetamine-induced hyperlocomotion, morphine-induced analgesia and diazepam-induced increased open arm exploration of rats on the elevated plus maze. These data are discussed in terms of (a) the possibility that serotoninergic mechanisms have a role in mediating reinforcement and (b) the relationship between appetitive properties and specific behavioral effects of psychostimulants, opiates and anxiolytics.

Analgesia↗

PubMed1988

Drug-induced place preference in rats with 5,7-dihydroxytryptamine lesions of the nucleus accumbens.

The conditioned place preference (CPP) paradigm was used to determine a role for serotonin in the nucleus accumbens in the mediation of the rewarding properties of D-amphetamine morphine and diazepam. The effect of these drugs on CPP was examined in controls and in animals with 5,7-dihydroxytryptamine lesions of the nucleus accumbans. The results from control animals confirmed that D-amphetamine (1.5 mg/kg, i.p.), morphine (2.0 mg/kg, i.p.) and diazepam (1.0 mg/kg, i.p.) produced place preference for a distinctive environment that had previously been paired with injections of the drug. In animals with 80% reduction of 5-hydroxytryptamine content of the nucleus accumbens, D-amphetamine CPP was unchanged and morphine CPP was attenuated compared with controls. Diazepam CPP was not apparent in animals with the lesion. In separate experiments, characteristic behavioural effects of the drugs under study were examined in control and in animals with lesion. The results showed a tendency for increased amphetamine hyperlocomotion, enhanced morphine activity and analgesia and decreased diazepam anti-anxiety effect in animals with lesions. Thus, the 5,7-dihydroxytryptamine lesions of the nucleus accumbens differently influenced the CPP induced by the drugs studied and, with the exception of diazepam, the various behavioural effects elicited by each drug. The findings suggest that serotonin-containing neurones of the nucleus accumbens are a component of the neural circuitry that mediates the rewarding properties of morphine, probably of diazepam, but not of D-amphetamine.

5,7-Dihydroxytryptamine↗

PubMed1988

Chronic antidepressant treatment increases the apomorphine-induced elevation of plasma corticosterone in rats.

Plasma corticosterone concentrations in response to subcutaneous administration of apomorphine (25 and 200 micrograms kg-1) have been assessed in rats treated acutely (2 days) or repeatedly (15 days) with saline, clomipramine, electroshock and clomipramine + electroshock. Chronic, but not acute, antidepressant treatment decreased the corticosterone level which remained unchanged in control and in rats acutely treated with apomorphine. Chronic antidepressant treatment significantly increased the corticosterone response to apomorphine. Neuroendocrine evidence is provided for an increased responsiveness of dopamine receptors which are thought to mediate the apomorphine effect on corticosterone secretion following chronic antidepressant treatment.

Animals↗

PubMed1987

Apomorphine-induced behaviour during the oestrous cycle of the rat.

The effect of various doses of apomorphine (APO) (25, 250, 400 and 750 micrograms/kg, s.c.) on open field behaviour, stereotyped behaviour, body temperature and concentrations of serum oestradiol was studied in cycling females and in ovariectomized rats. With the exception of grooming, the hormonal variations during the cycle, or the ovariectomy, did not have an effect on behaviour related to stimulation of presynaptic dopamine (DA) receptors. The endocrine status on proestrus (PE), characterized by an increase in serum oestradiol, did influence hyperlocomotion and hypothermia induced by apomorphine; the former being attenuated and the latter increased, as compared to the other phases of the cycle. Ovariectomy resulted in an increase in the stimulatory effect of apomorphine on locomotion. Stereotypy induced by apomorphine was unaltered by hormonal variations during the cycle and it was slightly attenuated by removal of the ovaries. During phases of low levels of oestrogen (oestrus, metestrus) apomorphine significantly increased the levels of serum oestradiol, determined 30 min after the administration of drug. It is concluded that the various DAergic mechanisms in brain are differentially affected by hormonal variations during the cycle and by ovariectomy.

Animals↗

PubMed1987

Estrogen treatment to ovariectomized rats modifies morphine-induced behavior.

Two weeks after surgery, ovariectomized (OVX) rats were treated for 3 days with either 17 beta-estradiol (10 or 100 micrograms/kg, SC, per day) or the oil vehicle. They were then tested for morphine-induced hyperactivity (4 mg/kg, IP), analgesia and catalepsy (15 and 20 mg/kg, IP) 24 or 72 hr after the last steroid or oil injection. Estradiol treatment did not affect the locomotion or the sensitivity to nociceptive stimuli of OVX rats and did not induce a cataleptic state in animals. Estradiol- (100 micrograms/kg) treated OVX rats exhibited attenuated morphine-induced hyperlocomotion regardless of the time that had elapsed after estradiol treatment cessation, attenuated morphine-induced catalepsy at 24 hr after estradiol treatment and unaltered morphine-induced analgesia. OVX rats treated with a lower estradiol dose (10 micrograms/kg) exhibited significantly increased morphine-induced analgesia and slightly increased catalepsy. The results show that the sensitivity of brain opiate systems controlling some of the behavioral effects of morphine is modified following estradiol treatment to OVX rats.

Analgesia↗

PubMed1987

Intravenous cocaine-induced place preference: attenuation by haloperidol.

Cocaine reward was demonstrated by establishing a conditioned place preference (CPP) to a distinctive location paired with cocaine administered either intravenously (i.v., 0.5 mg/kg) or intraperitoneally (i.p., 10 mg/kg). Significant i.p. or i.v. cocaine CPP was observed following the second conditioning trial. Haloperidol (0.2 mg/kg) pretreatment disrupted CPP induced by i.v., but not i.p., cocaine. The haloperidol effect built up over successive trials. The involvement of dopaminergic transmission in i.v. cocaine-induced CPP is discussed.

Animals↗

PubMed1986

Dopamine dependent behaviours in rats with bilateral ibotenic acid-induced lesions of the globus pallidus.

Amphetamine hyperactivity, apomorphine stereotypy and haloperidol catalepsy were studied in rats following selective damage to cell bodies within the globus pallidus (GP). Ibotenic acid-induced bilateral lesions of GP attenuated the spontaneous locomotion of rats, but they did not influence the locomotor response to amphetamine. Apomorphine-induced gnawing and licking but not sniffing were attenuated in rats with GP lesions. The effect of haloperidol on catalepsy was enhanced following the GP lesion. It is concluded that the normal expression of some dopamine-related functions depends to a great degree on the integrity of cells within the GP region.

Amphetamines↗

PubMed1985

Diazepam-induced place preference conditioning: appetitive and antiaversive properties.

The place conditioning paradigm was used to examine the reinforcing properties of diazepam. Rats were injected with diazepam (0.5-5.0 mg/kg, IP) and 30 min later were confined for 30 min to one side of a shuttle box, in which each of the two compartments had distinctive features. On alternate (control) days they received vehicle injections and were confined for 30 min to the opposite side. At almost all doses tested, diazepam produced place preference for the distinctive compartment that had been previously associated with the drug. Preference for the drug side developed regardless of whether diazepam was paired or unpaired with the least-preferred side, and regardless of whether testing was carried out in the undrugged or in the drugged state. The rats preferred the drug side over a novel compartment, but they did not change their initial preference for the side when diazepam was given after removal from the training box. Animals injected with meprobamate (70 mg/kg, PO), a non-benzodiazepine anxiolytic, also developed conditioned preference for the drug side, comparable to that seen following cocaine hydrochloride (10 mg/kg, IP). The diazepam (2.5 mg/kg)-induced place preference was antagonized by CGS 8216 (3 mg/kg, IP), picrotoxin (2 mg/kg, IP) and naloxone (0.8 mg/kg, SC), injected 3 min before and 15 and 20 min after diazepam respectively. Sodium valproate (200 mg/kg, IP) did not influence diazepam (1 mg/kg)-induced place preference. Sodium valproate by itself had marginal effects on place conditioning. Picrotoxin and naloxone, but not CGS 8816, produced place aversion which, in the case of picrotoxin, was due to state dependent learning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Chlorimipramine, electroconvulsive shock and combination thereof: differential effects of chronic treatment on apomorphine-induced behaviours and on striatal and mesocortical dopamine turnover.

We studied the influence of different pretreatment regimens (Chlorimipramine-Cmi, electroconvulsive shock-ECS, and Cmi + ECS all regimens being applied for either 2 or 15 days) on the open field behaviour, on the striatal and on the prefrontal dopamine-PFC DA turnover in rats injected with either apomorphine-AP 25 micrograms/kg (stimulating presynaptic DA receptors), AP 200 micrograms/kg (stimulating post-synaptic DA receptors), or vehicle (control). In the controls, AP 25 micrograms/kg reduced the locomotor activity and the striatal, but not the PFC DA turnover. AP 200 micrograms/kg increased the locomotor activity and reduced the striatal but not the PFC DA turnover. Short-term pretreatment: ECS and Cmi + ECS prevented the decrease of striatal DA turnover after AP 25 micrograms/kg. No other influence of any pretreatment on behaviour or DA-turnover became significant. Long-term pretreatment: Chronic Cmi: marginally increased the open field behaviour and marginally decreased the PFC DA turnover; significantly increased the effect of AP (200 micrograms/kg) on striatal DA turnover and the effect of AP (25 and 200 micrograms/kg) on PFC DA turnover. Repeated ECS: decreased locomotion and rearing and increased PFC DA turnover; increased the effect of AP (200 micrograms/kg) on locomotion and on striatal DA turnover; decreased the effect of AP (25 and 200 micrograms/kg) on PFC DA turnover. Chronic Cmi + ECS: decreased locomotion and rearing and marginally decreased PFC DA turnover; increased the effect of AP on hyperlocomotion and on striatal DA turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Acquisition and extinction of L-maze and conditioned avoidance behaviours following kainic acid-induced lesions of the ventromedial thalamic nuclei in rats.

Rats with kainic acid-induced lesions of the ventromedial thalamic (VMt) nucleus were compared with sham-operated controls on two behavioural tasks. The kainic acid injection resulted in loss of local neurons in the VMt nuclei with no appreciable damage to other thalamic nuclei or to other distant brain areas. VMt nuclei lesion animals learned to run in an L-maze for food reinforcement and to avoid electric foot-shock in the two way active avoidance shuttle-box procedure. Extinction of the food reinforced response was not altered by the lesion. One week retention of the acquired two-way active avoidance response was almost abolished on the animals with the lesion. Open field locomotion or escape latencies were not influenced by the lesion. It is concluded that VMt nuclei of rats are involved in the retention of aversively reinforced behaviours.

Animals↗

PubMed1983

Attenuation of heroin reward in rats by disruption of the mesolimbic dopamine system.

The rewarding properties of systemically administered heroin were investigated with a conditioned place-preference paradigm. Reinforcing effects were observed with all doses of heroin tested (0.5, 1.0, 2.0 mg/kg) as indicated by a significant increase in preference for the place paired with drug injections. No similar change in preference was observed following saline injections. The rewarding effect of heroin (2 mg/kg) was attenuated by pretreatment with haloperidol (0.2 mg/kg), but haloperidol alone did not produce a place aversion. Lesions induced by 6-hydroxydopamine (6-OHDA) of the mesolimbic dopaminergic pathway at the level of the nucleus accumbens also attenuated the heroin-induced place preference. In contrast, depletion of central and peripheral noradrenaline induced by 6-OHDA had no significant effect on heroin-induced place preference. These data suggest an important role for the mesolimbic DA system in mediating the reinforcing effects of heroin.

Animals↗

PubMed1982

Dopaminergic substrates of amphetamine-induced place preference conditioning.

The conditioned place preference paradigm was used to study the reinforcing properties of D-amphetamine. Rats were injected (i.p.) with D-amphetamine sulphate (0.5, 1.0 or 5.0 mg/kg) and 10 min later confined for 30 min to one side of a shuttle box in which each of the two compartments had distinctive features. On alternate (control) days they received saline injections and were confined for 30 min to the opposite side. At all doses D-amphetamine produced place preference for the distinctive compartment that previously had been associated with the drug. Pretreatment with haloperidol (0.15 or 1.0 mg/kg) antagonized the place preference produced by amphetamine (1.5 mg/kg). By itself, haloperidol (0.15 or 1.0 mg/kg) did not produce place aversion. In separate experiments the D-amphetamine-induced place preference was examined in rats that had received 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens. Animals with the greatest depletion of dopamine did not show preference for the compartment associated with D-amphetamine. Furthermore, the time spent on the amphetamine-reinforced side correlated significantly with the levels of dopamine remaining in the nucleus accumbens but not with the dopamine content in the striatum. Depletion of peripheral catecholamines by systemic injections of 6-OHDA did not affect D-amphetamine-induced place preference conditioning. Other groups of animals that received the dopamine receptor agonist, apomorphine, also developed a conditioned preference for the compartment that had been associated with the drug treatment. These findings support the view that the reinforcing effects of D-amphetamine are mediated by central dopamine-containing neurons, and in particular those of the mesolimbic system.

Animals↗

PubMed1982

Cocaine-induced place preference conditioning: lack of effects of neuroleptics and 6-hydroxydopamine lesions.

The conditioned place preference paradigm was used to investigate the reinforcing properties of cocaine. Rats were injected (i.p.) with cocaine hydrochloride (0.625-20 mg/kg) and then immediately confined for 30 min to one side of a shuttle box in which each of the two compartments had distinctive features. On alternate (control) days they received saline injections and were confined for 30 min to the opposite side. Cocaine produced a significant, dose-related preference for the distinctive environment that previously had been paired with the drug. Pretreatment with pimozide (0.5 or 1.0 mg/kg) or haloperidol (1.0 mg/kg), both of which blocked the locomotor stimulant effects of cocaine, failed to influence place preference produced by cocaine (5.0 mg/kg). In addition, neither 6-hydroxydopamine lesions of dopamine terminals in the nucleus accumbens nor 6-hydroxydopamine-induced destruction of central and/or peripheral noradrenergic systems affected cocaine-induced place preference conditioning. In other experiments it was found that injections of the local anaesthetic procaine, at doses that did not affect locomotor activity (25 and 50 mg/kg), also resulted in significant place preference conditioning. It is concluded that cocaine can produce place preference conditioning through a mechanism that is independent of its effects on catecholamine-containing neurons and that may be related to its local anaesthetic properties. It is noted, however, that if cocaine's local anaesthetic properties could be blocked selectively, the drug might still produce place preference conditioning through its enhancement of central dopaminergic function.

Animals↗

PubMed1982

Attenuation by haloperidol of place preference conditioning using food reinforcement.

The place preference conditioning paradigm was used to examine the reinforcing properties of food in hungry rats. Availability of food in one of two distinctive environments increased the amount of time they spent in the environment associated with food in a test when the animals were no longer food deprived and neither environment contained food. Pretreatment with haloperidol (0.1 or 0.2 mg/kg) during the conditioning phase blocked the establishment of place preference even though the animals consumed the food in the drugged state. The results are interpreted as demonstrating a role for dopamine-containing neurons in mediating the reinforcing properties of food.

Animals↗