Biomedical subjects

F Weiss

Publications and source records attributed to F Weiss.

At least 19 recordsLinked to original sources

PubMed1999

Ethanol exposure differentially alters central monoamine neurotransmission in alcohol-preferring versus -nonpreferring rats.

Individual differences in ethanol preference may be linked to differences in the functional activity of forebrain monoamine systems or their sensitivity to modification by ethanol. To test this hypothesis, basal extracellular concentrations of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens as well as the effects of repeated ethanol pretreatment on the basal release of these transmitters were examined in alcohol-preferring (P), alcohol-nonpreferring (NP), and genetically heterogeneous Wistar rats. All animals received i.p. injections of ethanol (1.0 g/kg) or saline for 5 consecutive days. Fifteen hours after the final pretreatment, basal extracellular concentrations and "in vivo extraction fraction" values for DA and 5-HT were determined by no-net-flux in vivo microdialysis. In ethanol-naive rats, significant line differences were observed with high basal 5-HT release in P rats, low 5-HT release in NP rats, and intermediate 5-HT levels in Wistar rats. No differences among groups were noted in basal DA release. Ethanol pretreatment decreased basal extracellular 5-HT levels in P rats whereas increasing 5-HT efflux was seen in the Wistar and NP lines. In addition, ethanol pretreatment increased extracellular DA concentrations in Wistar and P rats, but not in NP rats. The results confirm a relationship between the functional status of forebrain DA and 5-HT systems and ethanol preference or aversion. Moreover, the data suggest that ethanol exposure can alter basal DA and 5-HT in the nucleus accumbens and that vulnerability to ethanol-induced changes in monoamine neurotransmission may be a factor in genetically determined ethanol preference.

Alcohol Drinking↗

PubMed1998

Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens.

The opiate antagonist naltrexone suppresses ethanol-reinforced behavior in animals and decreases ethanol intake in humans. However, the mechanisms underlying these actions are not well understood. Experiments were designed to test the hypothesis that naltrexone attenuates the rewarding properties of ethanol by interfering with ethanol-induced stimulation of dopamine activity in the nucleus accumbens (NAcc). Simultaneous measures of the effects of naltrexone on dialysate dopamine levels in the NAcc and on operant responding for oral ethanol were used. Male Wistar rats were trained to self-administer ethanol (10-15%, w/v) in 0.2% (w/v) saccharin during daily 30 min sessions and were surgically prepared for intracranial microdialysis. Experiments began after reliable self-administration was established. Rats were injected with naltrexone (0.25 mg/kg, s.c.) or saline and 10 min later were placed inside the operant chamber for a 20 min waiting period with no ethanol available, followed by 30 min of access to ethanol. A transient rise in dialysate dopamine levels was observed during the waiting period, and this effect was not altered by naltrexone. Ethanol self-administration reliably increased dopamine levels in controls. Naltrexone significantly suppressed ethanol self-administration and prevented ethanol-induced increases in dialysate dopamine levels. Subsequent dose-effect analyses established that the latter effect was not merely a function of reduced ethanol intake but that naltrexone attenuated the efficacy of ethanol to elevate dialysate dopamine levels. These results suggest that suppression of ethanol self-administration by opiate antagonists is the result of interference with dopamine-dependent aspects of ethanol reinforcement, although possible additional effects via nondopaminergic mechanisms cannot be eliminated as a factor in opiate antagonist-induced reduction of ethanol intake.

Animals↗

PubMed1998

Serotonin1B receptor stimulation enhances cocaine reinforcement.

The effects of serotonin1B [5-hydroxytryptamine1B (5-HT1B)] receptor activation on cocaine reinforcement were investigated using intravenous cocaine self-administration by rats. The 5-HT1B receptor agonists 5-methoxy-3-1,2,3,6-tetrahydro-4-pyridinyl-1H-indole (RU 24969) (0.3-3 mg/kg), 3-(1,2,5, 6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP 94,253) (0.3-3 mg/kg), and 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3, 2-b]pyridine (CP 93,129) (3 and 10 micrograms, i.c.v.) each dose-dependently reduced the self-administration of a cocaine dose on the descending limb of the fixed-ratio 5 (FR-5) cocaine dose-effect function, in a manner similar to the effect produced by increasing the unit dose of cocaine. In addition, each of these 5-HT1B agonists lowered the threshold dose of cocaine that supported self-administration. These results are consistent with a 5-HT1B agonist-induced potentiation of cocaine reinforcement. On a progressive ratio schedule of reinforcement, RU 24969 and CP 94,253 dose-dependently (0.3-3 mg/kg) increased the highest completed ratio for cocaine self-administration, again by producing behavioral alterations similar to those induced by increasing the unit dose of cocaine. The effect of CP 94,253 was dose-dependently blocked by the 5-HT1B/1D receptor partial agonist 2'-methyl-4'-(5-methyl[1,2, 4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid[4-methodoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR 127, 935) (0.3-10 mg/kg) but was unaffected by the 5-HT1A receptor antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl- benzamide (p-MPPI; 1-10 mg/kg). Self-administration behavior was not maintained when either RU 24969 or CP 94,253 was substituted for cocaine, indicating that these 5-HT1B agonists do not produce significant reinforcing effects alone. Together, these findings indicate that 5-HT1B receptor stimulation facilitates the reinforcing properties of cocaine. These results are in opposition to recent findings with 5-HT1B receptor knock-out mice and may have important ontogenic implications in the area of drug abuse research.

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

PubMed1998

Simple microbore high-performance liquid chromatographic method for the determination of dopamine and cocaine from a single in vivo brain microdialysis sample.

A microbore chromatographic method for the analysis of both dopamine and cocaine from in vivo brain microdialysis samples is described. To eliminate the need for separate chromatographic systems for each analyte, post-column electrochemical and ultraviolet detection systems were arranged in series. The limit of quantitation for dopamine (5 fmol) was well within range for detecting dialysate concentrations of this neurotransmitter in rats which were in a baseline, drug-free state. The limit of quantitation for cocaine (0.5 pmol) was sufficient to detect brain cocaine levels following the peripheral administration of a low dose of this psychostimulant (5 mg/kg, i.p.). Estimates of dialysate dopamine and cocaine concentrations after 5, 10 and 20 mg/kg cocaine (i.p.) were in agreement with reports which utilized separate HPLC analyses for each analyte.

Animals↗

PubMed1998

Substance dependence as a compulsive behavior.

A compulsion to take a drug combined with a loss of control in limiting intake is the defining feature of substance dependence or addiction, and is the conceptual framework for the criteria of substance dependence or addiction outlined by the World Health Organization and the American Psychiatric Association. However, defining exactly what constitutes loss of control and compulsive drug taking at the level of animal models is a daunting task, and it is clear that no validated animal model exists for the whole syndrome of addiction. The present discussion redefines loss of control as a narrowing of the behavioral repertoire toward drug-seeking behavior and suggests that there are many sources of reinforcement that contribute to this behavioral focus on drug seeking. Evidence is presented demonstrating separate animal models for many of these sources of reinforcement as well as for most of the criteria for substance dependence. Evidence is also presented showing that the brain neurochemical systems involved in processing drug reward are altered by chronic drug exposure to contribute additional sources of reinforcement. Challenges for the future involve not only elucidation of the neurobiological substrates of the different behavioral components of addiction, but better animal models of these components with which to effect such studies.

Animals↗

PubMed1998

Neurocircuitry targets in ethanol reward and dependence.

Alcoholism is a complex behavioral disorder characterized by excessive consumption of ethanol, a narrowing of the behavioral repertoire toward excessive consumption, the development of tolerance and dependence, and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome. Recent work has begun to define the neurocircuits responsible for the two major sources of reinforcement key to animal models of excessive ethanol intake: positive and negative reinforcement. Ethanol appears to interact with ethanol-sensitive elements within neuronal membranes that convey the specificity of neurochemical action. Ethanol reinforcement appears to be mediated by an activation of GABA-A receptors, release of opioid peptides, release of dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic ethanol administration as reflected by opposite effects during acute ethanol withdrawal and by the recruitment of other neurotransmitter systems such as the stress neuropeptide corticotropin-releasing factor. Future challenges will include a focus on understanding how these neuroadaptive changes convey vulnerability to relapse in animals with a history of ethanol dependence.

Alcohol Drinking↗

PubMed1998

Estrous cycle effects on operant responding for ethanol in female rats.

Human females have been reported to be uniquely sensitive to the deleterious effects of ethanol, thus it is important to study the characteristics of and mechanisms underlying alcohol consumption that may be specific to females. Models of ethanol self-administration in female rats that take into consideration the estrous cycle have the potential to provide important information concerning these characteristics and mechanisms. The purpose of this study was to explore the effect of the cycle on ethanol self-administration using a limited access operant paradigm. Female Wistar rats were trained to lever press for 10% ethanol versus water using a saccharin fading procedure. Responses were examined across the four phases of the estrous cycle. No effects of estrous cycle phase were observed when these rats were allowed to cycle freely. Subsequently, estrous phase effects were investigated in females whose cycles had been synchronized. Under this condition, an effect of estrous phase was present, with lower ethanol intake observed in estrus (and in some cases proestrus). Synchronized rats all showed at least one very clear 4-day estrous cycle, whereas free-running rats' cycles ranged from 3 to 5 days. Thus, it is more likely that synchronized rats were tested in the identical portion of each phase, when hormone levels were less variable. These results suggest that ethanol may be more reinforcing during diestrus than proestrus and estrus in female rats.

Alcohol Drinking↗

PubMed1997

Opposite effects of stress on dopamine release in the limbic system of drug-naive and chronically amphetamine-treated rats.

The effects of repeated amphetamine administration on stress-induced dopamine release in the ventral striatum were examined in male Wistar rats treated with D-amphetamine (1.5 mg/kg; i.p./injection) or saline at 12 h intervals for 14 days. After 12 h as well as 7 days of amphetamine withdrawal, dopamine release was monitored by transverse microdialysis under basal conditions and during exposure to 60 min of restraint stress. Basal dopamine release was significantly suppressed relative to saline-pretreated controls after both 12 h and 7 days of amphetamine withdrawal. In control rats, restraint stress resulted in significantly increased dopamine efflux. In contrast, exposure to this stressor was associated with a significant suppression of dopamine release in rats chronically exposed to amphetamine. This effect was observed at both post-amphetamine test points. The results suggest that chronic amphetamine impairs the dopaminergic response to stress and that this dopaminergic deficit may play a role in stress-induced drug-seeking behavior and relapse.

Amphetamine↗

PubMed1997

Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal.

Corticotropin-releasing factor (CRF) has been implicated in the mediation of the stress-like and negative affective consequences of withdrawal from drugs of abuse, such as alcohol, cocaine, and opiates. This study sought to determine whether brain CRF systems also have a role in cannabinoid dependence. Rats were treated daily for 2 weeks with the potent synthetic cannabinoid HU-210. Withdrawal, induced by the cannabinoid antagonist SR 141716A, was accompanied by a marked elevation in extracellular CRF concentration and a distinct pattern of Fos activation in the central nucleus of the amygdala. Maximal increases in CRF corresponded to the time when behavioral signs resulting from cannabinoid withdrawal were at a maximum. These data suggest that long-term cannabinoid administration alters CRF function in the limbic system of the brain, in a manner similar to that observed with other drugs of abuse, and also induces neuroadaptive processes that may result in future vulnerability to drug dependence.

Amygdala↗

PubMed1997

Opponent process model and psychostimulant addiction.

There are many sources of reinforcement in the spectrum of cocaine dependence that contribute to the compulsive cocaine self-administration or loss of control of cocaine intake that constitutes the core of modern definitions of dependence. The development of withdrawal has long been considered an integral part of drug addiction but has lost its impact in the theorization of drug dependence because of new emphasis on the neurobiological substrates for the positive-reinforcing properties of drugs. The present treatise reviews the neurobiological substrates for the acute positive reinforcing effects of cocaine and what is beginning to be known about the neurobiological substrates of cocaine withdrawal. The concept of motivational or affective withdrawal is reintroduced, which reemphasizes opponent process theory as a model for the motivational effects of cocaine dependence. The same neural substrates hypothesized to be involved in the acute reinforcing properties of drugs (basal forebrain regions of nucleus accumbens and amygdala) are hypothesized to be altered during chronic drug treatment to produce the negative motivational states characterizing drug withdrawal. Within these brain regions, both the neurochemical system(s) on which the drug has its primary actions and other neurochemical systems may undergo adaptations to chronic presence of the drug. An understanding of the adaptations of the motivational systems of the brain accompanying cocaine dependence leads to important predictions not only about the etiology, treatment, and prevention of cocaine addiction but also about the vulnerability of these motivational systems in non-drug-induced psychopathology.

Animals↗

PubMed1997

Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission.

The mouse mutant coloboma (Cm/+), which exhibits profound spontaneous hyperactivity and bears a deletion mutation on chromosome 2, including the gene encoding synaptosomal protein SNAP-25, has been proposed to model aspects of attention-deficit hyperactivity disorder. Increasing evidence suggests a crucial role for SNAP-25 in the release of both classical neurotransmitters and neuropeptides. In the present study, we compared the release of specific neurotransmitters in vitro from synaptosomes and slices of selected brain regions from Cm/+ mice with that of +/+ mice. The release of dopamine (DA) and serotonin (5-HT) from striatum, and of arginine vasopressin and corticotropin-releasing factor from hypothalamus and amygdala is calcium-dependent. Glutamate release from and content in cortical synaptosomes of Cm/+ mice are greatly reduced, which might contribute to the learning deficits in these mutants. In dorsal striatum of Cm/+ mutants, but not ventral striatum, KCl-induced release of DA is completely blocked and that of 5-HT is significantly attenuated, suggesting that striatal DA and 5-HT deficiencies may be involved in hyperactivity. Further, although acetylcholine failed to induce hypothalamic corticotropin-releasing factor release from Cm/+ slices, restraint stress increased plasma corticosterone levels in Cm/+ mice to a significantly higher level than in +/+ mice, suggesting an important role for arginine vasopressin in hypothalamic-pituitary-adrenal axis activation. These results suggest that reduced SNAP-25 expression may contribute to a region-specific and neurotransmitter-specific deficiency in neurotransmitter release.

Acetylcholine↗

PubMed1996

Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats.

Basal forebrain dopamine (DA) and 5-HT neurotransmission has been implicated in the mediation of the acute reinforcing actions of ethanol. Neuroadaptation theories predict that compensatory changes in neurochemical systems that are activated by alcohol acutely may underlie symptoms of withdrawal after chronic administration. To test this hypothesis, the release of DA and 5-HT was monitored by microdialysis in the nucleus accumbens of dependent male Wistar rats at the end of a 3-5 week ethanol (8.7% w/v) liquid diet regimen, during 8 hr of withdrawal, and during renewed availability of ethanol involving (1) the opportunity to operantly self-administer ethanol (10% w/v) for 60 min, followed by (2) unlimited access to the ethanol-liquid diet. Results were compared to control groups pair-fed with ethanol-free liquid diet and trained to self-administer either ethanol or water. In nondependent rats, operant ethanol self-administration increased both DA and 5-HT release in the NAC. Withdrawal from the chronic ethanol diet produced a progressive suppression in the release of these transmitters over the 8 hr withdrawal period. Self-administration of ethanol reinstated and maintained DA release at prewithdrawal levels but failed to completely restore 5-HT efflux. 5-HT levels recovered rapidly, however, within 1 hr of reexposure to ethanol liquid diet. These findings suggest that deficits in accumbal monoamine release may contribute to the negative affective consequences ethanol withdrawal and, thereby, motivate ethanol-seeking behavior in dependent subjects.

Animals↗

PubMed1996

Sympathetic vasomotor dysfunction in leprosy patients: comparison with electrophysiological measurement and qualitative sensation testing.

Testing of skin vasomotor reflexes (VRs) by laser Doppler flowmetry (LDF) is now a recognised method of measuring peripheral dysautonomia. To assess its specificity as an indicator of impairment to unmyelinated autonomic fibres, VR testing at the fingerpulp was compared with standard qualitative sensation (QST) and with sensory electrophysiological (SNVC) measurements in 39 Iranian leprosy patients. There was a significant relationship between VR and SNCV values (but not QST): these were jointly measurable in 38.5% of fingers, and jointly absent in 35.3% of fingers which also showed significantly reduced LDF perfusion and skin temperatures. However, in 10.3% of fingers, predominantly index and otherwise apparently healthy, VRs were absent but SNCV present, suggesting early sub-clinical autonomic impairment. In a further 16% of fingers, predominantly ulnar and with poor microcirculation, intact (though impaired) VRs could be recorded despite the absence of SNCV responses, suggesting sparing or regeneration of these fibres. This evidence suggests that where there is heterogeneity of nerve damage a combination of VR and electrophysiological testing can indicate the functional status of distinct fibre types.

Adolescent↗

PubMed1996

Effects of dopamine agonists and antagonists on cocaine-induced operant responding for a cocaine-associated stimulus.

The present study examined the effects of receptor subtype-selective dopamine agonists and antagonists on (i) cocaine-induced responding for a cocaine-associated stimulus and (ii) on responding for food and cocaine reinforcement. Rats implanted with intravenous catheters were trained to lever-press for food or cocaine reinforcers on an FR5-FR5 multiple schedule, which was preceded by a 5-min component during which only stimuli previously associated with the primary reinforcers were available response-contingently. (i) Non-contingent delivery of cocaine at the beginning of the stimulus component significantly increased responding for the cocaine-associated stimulus, compared to responding for the food-associated cue. Changes in the dose of cocaine administered non-contingently before the stimulus component resulted in an inverted U-shaped dose-effect curve in responding for the cocaine-associated cue. In subsequent experiments, pretreatment with the dopamine D2 receptor agonist bromocriptine (4.0-16.0 mg/kg IP) attenuated the cocaine-induced increase in responding for the cocaine-associated cue. In contrast, pretreatment with low doses of SDZ 208-911, a dopamine D2 partial agonist (0.025-0.1 mg/kg SC), further potentiated the cocaine-induced response. Pretreatment with low and medium doses of the dopamine D1 and D2 receptor subtype-selective antagonists SCH 23390 (D1; 5-10 micrograms/kg SC) and raclopride (D2; 100-200 micrograms/kg SC) blocked responding for cocaine-associated cues, with SCH 23390 acting more selectively than raclopride. At higher doses (SCH 23390: 20 micrograms/kg SC; raclopride: 400 micrograms/kg SC), both drugs produced non-selective effects by inhibiting responses for the food-associated cue. (ii) Varying the dose of cocaine self-administered during the multiple schedule resulted in an inverted U-shaped dose-effect curve during the cocaine components, while the number of food pellets earned remained unchanged. Pretreatment with bromocriptine selectively reduced the number of cocaine infusions obtained. The compensatory increases in responding for cocaine typically associated with SCH 23390, raclopride or SDZ 208-911 pretreatment were also observed under the present schedule conditions, although the effect did not reach statistical significance in the case of SCH 23390 and raclopride, possibly due to methodological constraints. The results indicate that the present rat model of cocaine-seeking behavior is sensitive to pharmacological manipulations and may yield important information regarding the neurobiological mechanisms underlying conditioned and unconditioned reinforcing aspects of cocaine addiction.

Animals↗

PubMed1996

Serotonin1b receptor stimulation enhances dopamine-mediated reinforcement.

The effect of 5-HT1B receptor stimulation on dopamine-mediated reinforcement in rats was investigated using intravenous self-administration of the selective dopamine uptake inhibitor GBR-12909 on an FR5 schedule of reinforcement. Pretreatment with the 5-HT1A/1B receptor agonist CGS-12066B (1-10 mg/kg, IP) dose-dependently reduced the self-administration of GBR-12909 (83 micrograms/injection) by increasing the interval between drug injections, consistent with a enhancement of the reinforcing effects of GBR-12909. Additionally, CGS-12066B pretreatment (3 mg/kg, IP) shifted the dose-effect function for GBR-12909 self-administration to the left. Pretreatment with the selective 5-HT1A receptor agonist 8-OH-DPAT (0.03-1.0 mg/kg, SC) had no significant effect on GBR-12909 self-administration (83 micrograms/injection), indicating that the effect of CGS-12066B is not mediated by the 5-HT1A receptor. Finally, CGS-12066B pretreatment (1-10 mg/kg, IP) did not alter the self-administration of cocaine (0.03-0.5 mg/injection), suggesting that the simultaneous stimulation of multiple 5-HT receptor subtypes by the indirect 5-HT agonist properties of cocaine may mask the effect of 5-HT1B receptor stimulation on DA-mediated reinforcement.

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

PubMed1996

Extracellular serotonin is decreased in the nucleus accumbens during withdrawal from cocaine self-administration.

Many of the withdrawal symptoms reported by human cocaine users are thought to be correlated with serotonergic dysfunction. To explore the neurochemical basis for this hypothesis, we used in vivo microdialysis to monitor extracellular serotonin (5-HT) in the nucleus accumbens of the rat both during and for several hours after unlimited-access intravenous cocaine self-administration. Self-administration of cocaine produced an increase of approx. 340% of baseline in the dialysate concentration of 5-HT that persisted for the entire 12 h session. During the first 6 h after self-administration, dialysate 5-HT levels were significantly decreased to 41% of pre-session levels and 25% of the levels in drug-naive control animals. The effects of cocaine exposure on basal extracellular 5-HT concentrations were also examined using a quantitative microdialysis method (Difference Method). Rats withdrawing from extended-access cocaine self-administration displayed significantly lower extracellular 5-HT levels (0.6 +/- 0.3 nM) than either drug-naive control animals (2.0 +/- 0.5 nM) or animals which received daily 3-h self-administration training sessions only (limited-access; 1.4 +/- 0.2 nM). Together these results indicate that extracellular 5-HT is significantly decreased in the nucleus accumbens during withdrawal from cocaine self-administration. The severity of this decrease is contingent on the length of time cocaine is self-administered.

Animals↗

PubMed1996

Neurochemical evidence that postsynaptic nucleus accumbens D3 receptor stimulation enhances cocaine reinforcement.

The mechanism by which two D3 receptor-preferring agonists, 7-hydroxydipropylaminotetralin (7-OH-DPAT) and quinelorane, modulate cocaine reinforcement was examined by monitoring nucleus accumbens dopamine levels with in vivo microdialysis while rats intravenously self-administered the following four different drug solutions consecutively: (1) cocaine; (2) a combination of cocaine plus a low dose of either agonist; (3) either agonist alone; and finally, (4) a physiological saline solution. Both 7-OH-DPAT (4 micrograms/infusion) and quinelorane (0.25 microgram/infusion) decreased cocaine (0.25 mg/infusion) intake in a manner indicating an enhancement of cocaine reinforcement and simultaneously decreased the cocaine-induced elevations in nucleus accumbens dopamine levels by > 50%. Subsequent self-administration of either 7-OH-DPAT (4 micrograms/infusion) or quinelorane (0.25 microgram/infusion) alone resulted in significant, but stable, increases in drug intake, with a concurrent decrease in nucleus accumbens dopamine levels to approximately 50% below nondrug baseline levels. These findings indicate that postsynaptic D3 receptor stimulation in the nucleus accumbens enhances the reinforcing properties of cocaine. In a second experiment, local application of 7-OH-DPAT via reverse dialysis (30 and 100 nM perfusate concentrations) dose-dependently decreased nucleus accumbens dopamine efflux to 76 +/- 3.9 and 61 +/- 6.3% of baseline, respectively, whereas there was no effect of this agonist on dopamine efflux in the ipsilateral striatum of these same animals. Coperfusion with the D3 receptor-preferring antagonist nafadotride dose-dependently blocked the effect of 7-OH-DPAT on nucleus accumbens dopamine efflux. These results suggest that, at low concentrations, 7-OH-DPAT selectively activates D3 receptors in vivo.

Animals↗

PubMed1995

Sensitization of cocaine-stimulated increase in extracellular levels of corticotropin-releasing factor from the rat amygdala after repeated administration as determined by intracranial microdialysis.

Using intracranial microdialysis, the effect of repeated cocaine (30 mg/kg i.p.) versus saline administration for 10 consecutive days upon basal and stimulated release of corticotropin-releasing factor (CRF) was examined in the central amygdaloid nucleus (CeA) of anesthetized rats. No significant differences in basal CRF levels between daily cocaine and saline treated groups were found. However, after cocaine challenge (10 mg/kg i.p.) the increase in CRF overflow was significantly greater in cocaine- as opposed to saline-pretreated rats (266 +/- 55.4% versus 149 +/- 8.5% of basal levels). Local administration of 4-aminopyridine produced a significant increase in CRF efflux (195 +/- 58.5%) in daily cocaine-treated rats with only a weak response in the control group (127 +/- 30.9%). These data demonstrate that repeated administration of cocaine enhances cocaine-induced release of CRF in the rat CeA. The sensitization of CRF release may play a significant role in psychostimulant-induced sensitization phenomena.

Aminopyridines↗