Biomedical subjects

M T Bardo

Publications and source records attributed to M T Bardo.

At least 55 records · Page 3Linked to original sources

PubMed1997

(-)-Nornicotine partially substitutes for (+)-amphetamine in a drug discrimination paradigm in rats.

Rats were trained in a two-lever food-reinforced operant task to discriminate (+)-amphetamine (1 mg/kg) from saline. After discrimination training stabilized, test doses of (+)-amphetamine (0.0625-2.0 mg/kg), (-)-nicotine (0.1-1.0 mg/kg), or (-)-nornicotine (1-10 mg/kg) were assessed for their ability to substitute for the (+)-amphetamine training dose during brief test sessions in which food reinforcement was withheld. As expected, as the test dose of (+)-amphetamine increased, there was a dose-related increase in drug-appropriate responding, with both 1 and 2 mg/kg test doses substituting fully for the (+)-amphetamine training dose. Both (-)-nicotine and (-)-nornicotine showed partial substitution (approximately 50% drug-appropriate responding) for the (+)-amphetamine training dose, with (-)-nicotine being more potent than (-)-nornicotine. Rate suppressant effects prevented the assessment of higher doses of (-)-nicotine or (-)-nornicotine. Thus, while (-)-nicotine and (-)-nornicotine share similar discriminative stimulus properties, the mechanism that mediates this effect appears to differ, at least in part, from that activated by (+)-amphetamine.

Animals↗

PubMed1997

Transient increases in catecholaminergic activity in medial prefrontal cortex and nucleus accumbens shell during novelty.

Voltammetric recordings with electrochemically modified carbon-fiber electrodes were obtained from specific regions of the forebrain in rats given free-choice access to a novel environment. Entry into novelty increased the catechol signal in the medial prefrontal cortex and shell of the nucleus accumbens by more than 100%, but had no consistent effect in either the neostriatum or accumbal core. In both the medial prefrontal cortex and accumbal shell, moreover, the novelty-induced increase in catecholaminergic activity was detectable only during the initial entry into the novel compartment and did not reappear when animals returned to the familiar environment. These results support increasing evidence for a functional distinction between the accumbal core and shell, with the latter having been linked to brain reward mechanisms. The results also indicate that novelty activates, albeit very transiently, some of the same neurochemical systems believed to play a critical role in the reinforcing effects of certain drugs of abuse.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Individual differences in response to novelty, amphetamine-induced activity and drug discrimination in rats.

Rats were pre-tested in several individual difference screens--novelty-induced activity, novelty-induced place preference, novel-object interaction, and amphetamine-induced activity. Rats that were more sensitive to the locomotor effects of amphetamine were more active in an inescapable novel environment and displayed a greater preference for a novel environment. All animals were then trained to discriminate amphetamine (1 mg/kg) from saline in a two-bar discrimination procedure using food-maintained responding. After acquisition of the discrimination (mean = 37 trials), two amphetamine generalization tests (0.0625, 0.125, 0.25, 0.5, 1.0 and 2.0 mg/kg) were conducted. In the second generalization test, rats that were more sensitive to the activating effect of amphetamine were also more sensitive to the discriminative stimulus effects of amphetamine (i.e. lower median effective dose). Moreover, high responders in the novelty-induced activity and novelty-induced place preference screens were more sensitive than low responders to the bar-press suppressant effects of amphetamine in the first generalization test. The relationships are discussed in terms of identifying processes common to the screens (e.g. stress and reward).

Animals↗

PubMed1996

Repeated 7-OH-DPAT treatments: behavioral sensitization, dopamine synthesis and subsequent sensitivity to apomorphine and cocaine.

Male Wistar rats (250-350 g) were injected (SC) daily with the putative selective dopamine D3 receptor agonist, 7-OH-DPAT (0.01, 0.10, or 1.0 g/kg) or vehicle for 10 days. Fifteen minutes after each injection, the rats were tested for locomotor activity in photocell arenas for 20 min or 2 h. In two experiments, following this subchronic treatment, all rats received a challenge injection of apomorphine (1.0 mg/kg, SC), or cocaine (10 mg/kg, IP) on day 11, and were tested for locomotor activity. In a third experiment, dopamine synthesis in striatal and mesolimbic (nucleus accumbens-olfactory turbercle) tissue was assessed following acute or chronic 7-OH-DPAT treatments by measuring the accumulation of dihydroxyphenylalanine (DOPA) after treatment with a DOPA decarboxylase inhibitor. Major findings were as follows: a) acute 7-OH-DPAT treatment produced a dose-dependent decrease in locomotor activity; b) when tested for 2 h, the 1.0 mg/kg dose of 7-OH-DPAT produced a progressively greater increase in activity across the 10 test days (i.e., behavioral sensitization); c) subchronic treatment with 7-OH-DPAT did not result in cross-sensitization to either apomorphine or cocaine; d) acute treatment with the 1.0 mg/kg dose of 7-OH-DPAT significantly decreased dopamine synthesis in both striatal and mesolimbic regions; and e) chronic 7-OH-DPAT treatments did not affect basal dopamine synthesis in either brain region. Although the behavioral effects of 7-OH-DPAT were similar to the reported effects of the D2/D3 dopamine agonist quinpirole, the effects of repeated 7-OH-DPAT treatments differed from those of quinpirole in terms of cross-sensitization and basal dopamine synthesis. These results suggest that locomotor inhibition produced by low doses of 7-OH-DPAT is not related to dopamine autoreceptor stimulation, and the development of behavioral sensitization to high doses of 7-OH-DPAT is not due to the development of dopamine autoreceptor subsensitivity.

Animals↗

PubMed1996

Characterization of the conditioned taste aversion produced by 7-OH-DPAT in rats.

Using the conditioned taste aversion preparation, we described the dose-effect curve for the reputed dopamine D3 agonist (+/-)7-OH-DPAT (0, 0.001, 0.01, 0.1, 1.0, or 10 mg/kg). Rats received a 0.1% saccharin taste paired on repeated occasions with one of the 7-OH-DPAT doses. The 0.1, 1.0, and 10.0 mg/kg doses of 7-OH-DPAT produced a significant conditioned saccharin aversion. This aversion was evident regardless of whether saccharin intake of 7-OH-DPAT-treated rats was compared to their own water consumption or to saccharin intake by saline-treated rats.

Animals↗

PubMed1996

Psychobiology of novelty seeking and drug seeking behavior.

There is considerable evidence that high novelty seekers are at increased risk for using drugs of abuse relative to low novelty seekers. This review examines the potential biological mechanism that may help explain the relationship between novelty seeking and drug seeking behavior. Evidence is summarized to suggest that exposure to novelty activates, at least in part, the same neural substrate that mediates the rewarding effects of drugs of abuse. It is argued that individual differences in response to novelty and drugs may relate to individual differences in the mesolimbic dopamine (DA) system of the brain. Individual differences in both novelty seeking and drug seeking behavior, while under some degree of genetic control, appear to be modifiable by early development experiences and this modification may relate to alterations in activity of the mesolimbic DA system. Within the context of this biological formulation, implications for the prevention and treatment of drug abuse are discussed.

Animals↗

PubMed1995

Ascorbate potentiates amphetamine-induced conditioned place preference and forebrain dopamine release in rats.

In order to evaluate the effects of ascorbate, which is known to modulate dopamine neurotransmission, on the reinforcing effects of amphetamine, we coadministered ascorbate and amphetamine during the acquisition of conditioned place preference (CPP) in rats. Our results indicate that 100 mg/kg ascorbate potentiates the CPP induced by 0.5 mg/kg, but not 1.0 mg/kg, amphetamine. A higher dose of ascorbate (500 mg/kg) did not influence the CPP induced by either dose of amphetamine. In vitro release assays revealed that, whereas ascorbate alone (0.01-1.0 mM) did not influence striatal dopamine levels, this vitamin potentiated amphetamine-induced dopamine release in both the nucleus accumbens and neostriatum. Collectively, these results raise the possibility that ascorbate potentiates amphetamine-induced CPP by increasing the ability of this psychostimulant to release dopamine.

Amphetamine↗

PubMed1995

Repeated quinpirole treatment: locomotor activity, dopamine synthesis, and effects of selective dopamine antagonists.

Repeated treatment with the non-selective dopamine agonist apomorphine results in behavioral sensitization and enhanced dopamine synthesis in dopamine projection fields. To examine the role of D2-type dopamine receptors in modulating these effects, the present experiment assessed the effects of repeated treatment with the D2-type agonist quinpirole on locomotor activity and dopamine synthesis. In the first experiment, rats were treated with vehicle or one of two doses (0.3 or 3.0 mg/kg) of quinpirole for 8 days. Daily measures of locomotor activity revealed an initial suppression of activity produced by quinpirole which dissipated over the 8 days of treatment. A trend for an increase in activity for 3.0 mg/kg quinpirole compared to vehicle was obtained on day 8. Twenty-four hours after cessation of treatment, dopamine synthesis, measured as accumulation of 3,4-dihydroxyphenylalanine (DOPA) after treatment with the DOPA decarboxylase inhibitor NSD-1015, was enhanced in the striatum, but not nucleus accumbens-olfactory tubercle (NAOT) or ventral mesencephalon (VM). In Experiment 2, rats were treated for 8 days with vehicle, 3.0 mg/kg quinpirole or the D1 antagonist SCH 23390 (0.5 mg/kg) in a two (vehicle or quinpirole) x two (vehicle or SCH 23390) design. Quinpirole-alone treatment resulted in a reduction of the locomotor suppressant effects of the drug. SCH 23390-alone and quinpirole-SCH 23390 combined treatment resulted in decreased activity compared to the vehicle control group that did not change across days. DOPA accumulation was enhanced in the striatum and NAOT after quinpirole treatment; however, SCH 23390 had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Conditioned place preference using opiate and stimulant drugs: a meta-analysis.

A meta-analysis was conducted on the data obtained from published articles that have used the conditioned place preference (CPP) paradigm to assess the rewarding effects of morphine, heroin, amphetamine and cocaine in rats. Using a histogram analysis of the data, significant dose-effect curves were evident with all of the drugs examined, except for cocaine. Analysis of the data also revealed that several methodological variables moderated the effect size for CPP, at least with some of the drugs examined. In particular, the following methodological variables significantly moderated CPP effect size: strain of rat used; housing condition (single or group cages); type of apparatus (2 or 3 compartments); preconditioning test (present or absent); route of drug administration; intervening saline trials (present or absent); conditioning trial duration; and drug compartment (nonpreferred, counterbalanced or white). No significant effect size differences were evident using sex, number of drug trials, or test duration as moderator variables in the analyses. These meta-analytic results may be useful to investigators for maximizing the effect size of drug-induced CPP.

Animals↗

PubMed1994

Age-dependent differences in the rate of recovery of striatal dopamine D1 and D2 receptors after inactivation with EEDQ.

Recovery of striatal dopamine D1 and D2 binding sites in 10-, 16-, and 39-day-old rats was measured 1, 2, 4, and 8 days after irreversible antagonism with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Ontogenetic and EEDQ-induced changes in D1 and D2 binding sites were determined by Scatchard analyses using six concentrations of either [3H]SCH 23390 or [3H]spiperone. Twenty-four hours after EEDQ (7.5 mg/kg) treatment, a significant depletion of both dopamine D1 and D2 receptors was found for all age groups; however, the magnitude of the depletion was greater in 39-day-old rats than in the two preweanling age groups. Both 16- and 39-day-old rats showed significant recovery of dopamine D1 and D2 receptors by the eighth day after EEDQ treatment, but the 16-day-old rats showed a faster recovery of dopamine D1 receptors than did the 39-day-olds. Unexpectedly, 10-day-old rats did not show any evidence of receptor recovery, as the percent control values for these animals did not change across the 8-day recovery period. Pretreatment with the dopamine D1 receptor antagonist SCH 23390 and the dopamine D2 receptor antagonist sulpiride was sufficient to protect dopamine D1 and D2 receptors from EEDQ-induced inactivation. Protein values and receptor affinity (pKd values) were not affected by EEDQ treatment at any of the ages tested. Therefore, these results indicate that the rate of dopamine receptor repopulation varies across ontogeny, with 10-day-old rats exhibiting slower recovery than older rat pups or postweanling rats.

Aging↗

PubMed1994

Morphine-conditioned analgesia using a taste cue: dissociation of taste aversion and analgesia.

The present study examined the ability of a taste cue to serve as a conditioned stimulus (CS) for conditioning the analgesic effect of morphine. Rats were given three pairings of a taste CS with a morphine unconditioned stimulus (US). As expected, there was a decrease in CS intake across repeated pairings, indicating that a conditioned taste aversion was obtained. More important, presentation of the CS alone also increased paw-lick latencies on a hot plate test (either 50 degrees C or 54 degrees C hot plate), suggesting that an analgesic conditioned response (CR) was obtained. The dose of morphine required to produce conditioned analgesia was higher than the dose of morphine required to produce conditioned taste aversion. Using 15 mg/kg morphine, however, both conditioned taste aversion and conditioned analgesia were present when the morphine US was given immediately following CS intake, but not when given 6 h following CS intake. In contrast to morphine, pairing a taste CS with lithium produced a conditioned taste aversion without any conditioned analgesic response. These results indicate that acquisition of an analgesic CR is not the result of stress induced by an aversion to the taste CS.

Analgesia↗

PubMed1994

Ontogenetic effects of EEDQ on amphetamine-induced behaviors of rats: role of presynaptic processes.

Previous research has shown that the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) affects dopamine (DA) synthesis and metabolism in both preweanling and adult rats. In the present study, we attempted to determine the behavioral relevance of EEDQ's presynaptic actions. To that end, 17- and 90-day-old rats were injected with either EEDQ (7.5 mg/kg, IP) or its vehicle 30 min after half the rats were pretreated with the selective DA antagonists SCH 23390 and sulpiride. (SCH 23390/sulpiride pretreatment was used to protect D1 and D2 receptors from EEDQ-induced inactivation.) The behavioral effects of amphetamine (0, 0.1, 0.3 or 1.0 mg/kg, IP) were then assessed 1, 2, 4, and 8 days after EEDQ treatment. Amphetamine-induced behaviors were used to assess EEDQ's presynaptic actions, because amphetamine does not directly bind to the DA receptor, but rather releases DA from the presynaptic terminal. Further, since half of the EEDQ-treated rats had a full complement of DA receptors (i.e., those rats pretreated with SCH 23390/sulpiride), EEDQ's actions in the presynaptic terminal could be dissociated from actions at pre- and postsynaptic receptors. In general, the results showed that EEDQ blocked most of the amphetamine-induced behaviors of both 17- and 90-day-old rats. Surprisingly, pretreatment with SCH 23390 and sulpiride only protected the amphetamine-induced behaviors of adult rats, but not the behaviors of 17-day-old rat pups. When considered together, these results suggest that EEDQ's presynaptic effects are not behaviorally relevant to the adult rat, but may be responsible for eliminating amphetamine-induced behaviors in the 17-day-old rat pup.

Aging↗

PubMed1994

Effects of EEDQ on the synthesis and metabolism of dopamine in preweanling and adult rats.

Ontogenetic differences in dopamine (DA) synthesis and metabolism were assessed in 17- and 90-day-old rats injected i.p. with the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) 24 hr prior to sacrifice. DA synthesis was determined by measuring DOPA accumulation after NSD-1015 induced inhibition of DOPA decarboxylase; whereas, DA turnover was estimated by measuring DA accumulation and DOPAC efflux after pargyline induced inhibition of monoamine oxidase. In addition, some of the rats were pretreated with the competitive D1 and D2 antagonists SCH 23390 (1.0 mg/kg) and sulpiride (100 mg/kg) in order to protect these receptor subtypes from EEDQ-induced inactivation. The latter procedure was used to determine whether EEDQ's presynaptic effects were mediated by D1 and D2 receptors or were nonspecific. The results showed that 7.5 mg/kg EEDQ increased the striatal DA synthesis of both preweanling and adult rats: effects eliminated if D1 and D2 receptors were protected by pretreatment with SCH 23390 and sulpiride. Striatal DA levels of both age groups were depressed by EEDQ treatment, while DA accumulation was unaffected. Age-dependent effects were apparent however, as 7.5 mg/kg EEDQ increased the DOPAC turnover of adult, but not 17-day-old rats. The inability of EEDQ to affect the DOPAC turnover of the younger rats was apparently not dose related, as 15 mg/kg EEDQ did not affect the striatal DOPAC turnover of 17-day-olds. In adult rats, the EEDQ-induced increase in DOPAC turnover was not mediated by DA receptors, as pretreatment with SCH 23390 and sulpiride did not block EEDQ's effects.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Dissociation of buprenorphine-induced locomotor sensitization and conditioned place preference in rats.

The locomotor and rewarding effects of the opioid mixed agonist-antagonist buprenorphine were assessed in a conditioned place preference (CPP) experiment. Separate groups of rats were given one of three doses of buprenorphine (0.3, 1.0 or 3.0 mg/kg) or saline paired with the white compartment of a CPP apparatus. The following day, all rats received saline paired with the black compartment. After six conditioning trials, rats were given free access to all compartments of the CPP apparatus. Horizontal activity data obtained during conditioning revealed increased activity (i.e., behavioral sensitization) for the three doses on trial 6. Vertical activity data revealed significant increases on trial 6 for the 1.0 and 3.0 mg/kg doses only. Significant CPP was obtained with the 0.3 mg/kg and 1.0 mg/kg doses of buprenorphine, but not with the 3.0 mg/kg dose. These data indicate that buprenorphine elicits locomotor sensitization after repeated exposures that follows a linear dose-response relationship. In contrast, these data suggest that the rewarding effects of buprenorphine follow an inverted U-shaped dose-response curve.

Animals↗

PubMed1994

Locomotor and rewarding effects of amphetamine in enriched, social, and isolate reared rats.

This study examined the influence of environmental enrichment on the behavioral response to amphetamine. Beginning at 21 days of age, rats were raised in one of three different environmental conditions: a) an enriched condition (EC), in which animals were caged in groups and provided with novel objects daily; b) a social condition (SC), in which animals were caged in groups without any novel objects; and c) an isolated condition (IC), in which animals were caged individually without any novel objects. At 53 days of age, animals from each environmental condition were assessed for amphetamine-induced changes in locomotor activity and reward using the conditioned place preference (CPP) paradigm. Results from saline-injected control animals indicated that EC animals exhibited less vertical activity than IC animals when exposed to the CPP apparatus. When challenged with amphetamine (0.5 or 2.0 mg/kg), there were no significant differences between SC and IC animals in either locomotor behavior or CPP. However, EC animals exhibited more horizontal and vertical activity following amphetamine than both the SC and IC animals. Similarly, EC animals exhibited a greater magnitude of amphetamine-induced CPP than both the SC and IC animals.

Amphetamine↗

PubMed1993

Neurochemical correlates of behavioral sensitization following repeated apomorphine treatment: assessment of the role of D1 dopamine receptor stimulation.

Previous research has revealed a role of repeated D1 dopamine receptor stimulation in the development of behavioral sensitization to the D1/D2 agonist apomorphine. The present experiments assessed the role of repeated D1 receptor stimulation in neurochemical changes accompanying locomotor sensitization to apomorphine. To assess direct effects of D1 stimulation on dopamine synthesis, rats were injected with the D1 agonist SKF 38393 (8 mg/kg), followed by an injection with the 3,4-dihydroxyphenylalanine (DOPA) decarboxylase inhibitor, NSD-1015. DOPA accumulation, assessed in striatal, nucleus accumbens-olfactory tubercle (NAOT), and ventral mesencephalon (VM) tissue samples, was not affected by acute SKF 38393. In the second experiment, rats were treated with 10 daily injections of vehicle, apomorphine (5 mg/kg) or the D1 agonist SKF 38393 (8 or 16 mg/kg). Daily measures of locomotor activity demonstrated a progressive increase in the apomorphine-treated rats, but not the SKF 38393-treated rats, across the 10 days. On day 11, all rats were injected with NSD-1015 for measurement of DOPA accumulation. Dopamine synthesis was enhanced in the striatum after repeated apomorphine treatment. In contrast, repeated SKF 38393 treatment resulted in either a small decrease or no change in DOPA accumulation in the different brain regions (striatum, NAOT, VM). In the third experiment, tissue levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and [3H]SCH 23390 binding to D1 receptors were measured in rats treated with 10 daily injections of vehicle, apomorphine (5 mg/kg), or SKF 38393 (16 mg/kg). In the striatum and NAOT, none of the repeated drug treatments had an effect on DOPAC or dopamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1993

The effect of environmental enrichment on amphetamine-stimulated locomotor activity, dopamine synthesis and dopamine release.

In two separate experiments, rats were raised in either an enriched condition (EC) or impoverished condition (IC) from 21 to 60 days of age. Experiment 1 assessed amphetamine-stimulated locomotor activity and in vivo dopamine (DA) synthesis and metabolism in the nucleus accumbens (NA) and striatum (Str). In Experiment 2, amphetamine-stimulated DA release in the NA and Str was assessed in vitro. The results showed that EC rats have lower basal levels of locomotor activity than IC rats. However, in the presence of amphetamine, EC rats showed a greater increase in locomotion over IC when compared to their own controls. Concomitant with this behavioral difference, EC rats also showed an enhanced neurochemical response to amphetamine in vivo. That is, relative to IC rats, amphetamine produced a greater synthesis of DA in the Str of EC rats, as well as a greater metabolism of DA in the NA of EC rats. In the in vitro DA release experiment, EC rats had a lower concentration of tissue DA than IC. However, in contrast to the in vivo experiment, there were no significant differences between EC and IC rats in amphetamine-stimulated release of DA in vitro in either the Str or NA. The failure of amphetamine to produce differential neurochemical effects in EC and IC rats in vitro may be because this experiment eliminated either pharmacokinetic effects or neurochemical differences in brain regions outside the NA and Str.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Opioid modulation of amphetamine-stimulated dopamine release and concentration in rat striatal slices.

The effects of morphine and naltrexone on amphetamine-stimulated release and total concentration of dopamine (DA) from rat striatal slices in vitro were examined in this study. Adult male Sprague-Dawley rats were sacrificed and the striata were dissected, sliced, and then incubated in buffer solution at 37 degrees C with amphetamine in the presence or absence of various concentrations of morphine, naltrexone (or both), or the dihydroxyphenylalanine (DOPA) decarboxylase inhibitor (NSD-1015). The concentrations of DOPA, DA, and dihydroxyphenylacetic acid (DOPAC) in the tissue slices and buffer media were measured by HPLC/EC. Amphetamine enhanced DA release and also increased total DA concentrations. However, neither morphine nor naltrexone alone altered DA concentration in the media or tissue slices relative to control (no drug added). Moreover, neither morphine nor naltrexone at 1, 10, or 100 microM altered amphetamine-stimulated DA release. However, morphine (1 or 10 microM) inhibited the amphetamine-stimulated increase in total concentration of DA. This effect of morphine was blocked by naltrexone. NSD-1015 alone or in combination with morphine did not alter amphetamine-stimulated DA release, but significantly reduced DA concentration in striatal slices. NSD-1015 alone also increased DOPA accumulation in both media and tissue slices, and this effect was inhibited by the addition of morphine. These results indicate that morphine inhibits the amphetamine-stimulated increase in total DA content, but not the amphetamine-stimulated release of DA.

3,4-Dihydroxyphenylacetic Acid↗