Biomedical subjects

C D Blaha

Publications and source records attributed to C D Blaha.

At least 19 recordsLinked to original sources

PubMed2005

Midbrain muscarinic receptors modulate morphine-induced accumbal and striatal dopamine efflux in the rat.

Midbrain dopamine neurons are critical in mediating the rewarding effects of opiates in dependent rats, as well as modulating some manifestations of opiate withdrawal. Morphine is known to excite dopamine neurons and thereby facilitate forebrain dopamine transmission through inhibition of GABA neurons. Cholinergic neurons in the mesopontine laterodorsal and pedunculopontine tegmental nuclei provide the principal source of excitatory cholinergic input to ventral tegmental area and substantia nigra pars compacta dopamine-containing neurons, via actions on midbrain muscarinic and nicotinic acetylcholine receptors. The present study hypothesized that a reduction in tonic cholinergic input via blockade of midbrain muscarinic receptors would reduce the pharmacological effects of morphine on forebrain dopamine release. Using in vivo chronoamperometry, alterations in morphine-evoked dopamine efflux were monitored at stearate-graphite paste electrodes implanted unilaterally in the nucleus accumbens and striatum of urethane (1.5 g/kg) anesthetized rats, following the pharmacological inhibition of ventral tegmental area/substantia nigra pars compacta muscarinic receptors. The facilitatory effects of morphine (2.0 mg/kg, i.v.) on accumbens and striatal dopamine efflux were markedly reduced by prior infusion of the non-selective muscarinic receptor antagonist scopolamine (200 microg/microl) into the ventral tegmental area or substantia nigra pars compacta, respectively. These findings demonstrate that decreased activation of midbrain muscarinic receptors attenuates the excitatory effects of morphine on mesoaccumbens and nigrostriatal dopaminergic transmission.

Animals↗

PubMed2004

An examination of d-amphetamine self-administration in pedunculopontine tegmental nucleus-lesioned rats.

The pedunculopontine tegmental nucleus (PPTg) has long been suggested to have a role in reward-related behaviour, and there is particular interest in its possible role in drug reward systems. Previous work found increased i.v. self-administration (IVSA) of d-amphetamine following PPTg lesions when training had included both operant pre-training and priming injections. The present study examined the effect of excitotoxin lesions of the PPTg on d-amphetamine IVSA under three training conditions. Naive: no previous experience of d-amphetamine or operant responding. Pre-trained: given operant training with food before lesion surgery took place. Primed: given single non-contingent d-amphetamine infusion (0.1 mg/0.l ml) at the start of each session. Rats in all conditions were given either ibotenate or phosphate buffer control lesions of the PPTg before d-amphetamine (0.1 mg/0.1 ml infusion) IVSA training took place. Rats received eight sessions of training under a fixed ratio (FR2) schedule of d-amphetamine IVSA, followed by four sessions under a progressive ratio (PR5) schedule. In the naive condition, PPTg-lesioned rats were attenuated in their responding under FR2, and took significantly fewer infusions under PR5 than the control group. Under FR2 in the pre-trained condition, there was no difference between PPTg excitotoxin and control lesioned rats; however, PPTg-lesioned rats took significantly fewer infusions under the PR5 schedule. In the primed condition, there were no differences between PPTg-lesioned and control rats under either FR2 or PR5 schedules. These data demonstrate that operant training prior to PPTg lesion surgery corrects some, but not all, of the deficits seen in the naive condition. PPTg-lesioned rats in both naive and pre-trained conditions showed reduced responding for d-amphetamine under a PR5 schedule. These deficits are overcome by priming with d-amphetamine. We suggest that alterations in striatal dopamine activity following PPTg lesions underlie these effects.

Analysis of Variance↗

PubMed2002

Excitotoxic lesions of the pedunculopontine differentially mediate morphine- and d-amphetamine-evoked striatal dopamine efflux and behaviors.

Cholinergic and glutamatergic cells in the pedunculopontine tegmental nucleus are a principal source of excitatory input to midbrain dopamine neurons projecting to the striatum. Disruption of these brainstem inputs has been shown to respectively enhance and reduce psychostimulant and opiate self-administration in rats. In the present study, d-amphetamine- and morphine-induced behaviors and dorsal striatal dopamine efflux, measured using in vivo chronoamperometry, were investigated 21 days after bilateral excitotoxic (ibotenate) lesions of the pedunculopontine in rats. Compared to sham-operated controls, pedunculopontine lesions enhanced stereotyped behaviors induced by a challenge injection of d-amphetamine (1.5 mg/kg, i.p.) to an extent that markedly interfered with the expression of locomotor behavior. A significant augmentation in striatal dopamine efflux was also observed in these lesioned animals under urethane anesthesia in response to a similar challenge injection of d-amphetamine (1.5 mg/kg, i.v.) 2 days following these behavioral observations. In direct contrast, pedunculopontine lesions in a separate group of rats significantly attenuated morphine-induced (2 mg/kg, i.p.) stereotyped activity, although no significant differences were observed in locomotion compared to sham-operated animals. Under urethane anesthesia, these lesions attenuated striatal dopamine efflux evoked by a similar challenge injection of morphine (2 mg/kg, i.v.). These findings indicate that the pedunculopontine differentially mediates the pharmacological actions of two diverse drugs of abuse on striatal dopamine neurotransmission and resultant behaviors. These results also imply that the pedunculopontine tegmental nucleus may serve as a major striatal-motor interface in the processing of salient environmental stimuli, and their incentive rewarding impact on dopamine-mediated behavioral responses.

Animals↗

PubMed2002

Effects of laterodorsal tegmentum excitotoxic lesions on behavioral and dopamine responses evoked by morphine and d-amphetamine.

Cholinergic and glutamatergic projections from the laterodorsal tegmental nucleus (LDT) in the rat pons excite midbrain dopamine cells to directly modulate forebrain dopamine transmission. We show that LDT-lesioned rats express higher intensity stereotypy (including orofacial movements), and higher levels of accumbal dopamine release in response to d-amphetamine (1.5 mg/kg), as compared to sham-operated rats. In contrast, LDT-lesioned rats showed decreased stereotypy and attenuated accumbal dopamine efflux as compared to sham animals, in response to morphine (2.0 mg/kg). These results suggest that the LDT plays a critical role in mediating motoric and neurochemical effects of diverse drugs of abuse, and that the pharmacology of the drug may critically determine whether its efficacy will be enhanced or attenuated by alterations in LDT activity. We conclude that the LDT has functional connections with the nigrostriatal dopamine system to affect drug-evoked stereotypy, which has implications for motoric disorders that are characterized by nigrostriatal dysfunction.

Analgesics, Opioid↗

PubMed2001

Dopamine D1 and NMDA receptors mediate potentiation of basolateral amygdala-evoked firing of nucleus accumbens neurons.

Interactions between the basolateral amygdala (BLA) and the nucleus accumbens (NAc) mediate reward-related processes that are modulated by mesoaccumbens dopamine (DA) transmission. The present in vivo electrophysiological study assessed: (1) changes in the firing probability of submaximal BLA-evoked single neuronal firing activity in the NAc after tetanic stimulation of the BLA, and (2) the functional roles of DA and NMDA receptors in these processes. Tetanic stimulation of the BLA potentiated BLA-evoked firing activity of NAc neurons for a short duration ( approximately 25 min). This short-term potentiation was associated with an increase in DA oxidation currents that was monitored with chronoamperometry. Systemic or iontophoretic application before BLA tetanus of the D(1) receptor antagonist SCH23390, but not the D(2) receptor antagonist sulpiride, abolished the potentiation of BLA-evoked NAc activity, whereas administration of SCH23390 3 min after tetanus had no effect. However, systemic administration of the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), either before or after BLA tetanus, abolished the potentiation of BLA-evoked firing of NAc neurons. These data suggest that higher-frequency activity in BLA efferents can autoregulate their excitatory influence over neural activity of NAc neurons by facilitating the release of DA and activating both DA D(1) and NMDA receptors. This may represent a cellular mechanism that facilitates approach behaviors directed toward reward-related stimuli that are mediated by BLA-NAc circuitries.

Amygdala↗

PubMed2001

Modulation of hippocampal and amygdalar-evoked activity of nucleus accumbens neurons by dopamine: cellular mechanisms of input selection.

Inputs from multiple sites in the telencephalon, including the hippocampus and basolateral amygdala (BLA), converge on neurons in the nucleus accumbens (NAc), and dopamine (DA) is believed to play an essential role in the amplification and gating of these different limbic inputs. The present study used extracellular single-unit recordings of NAc neurons in combination with chronoamperometric sampling of mesoaccumbens DA efflux to assess the importance of DA in the integration of different limbic inputs to the NAc. Tetanic stimulation of the fimbria potentiated hippocampal-evoked firing activity of NAc neurons and increased DA extracellular levels. Systemic administration of the D(1) receptor antagonist SCH23390 or the NMDA receptor antagonist CPP abolished the potentiation of hippocampal-evoked activity and produced a D(2) receptor-mediated suppression of evoked firing. In neurons that received converging input from the hippocampus and BLA, fimbria tetanus potentiated hippocampal-evoked firing activity and suppressed BLA-evoked activity in the same neurons. Both D(1) and NMDA receptors participated in the potentiation of fimbria-evoked activity, whereas the suppression of BLA-evoked activity was blocked by either D(1) receptor antagonism with SCH23390 or the adenosine A(1) antagonist 8-cyclopentyl-1,2-dimethylxanthine. Coincidental tetanus of both the fimbria and BLA resulted in potentiation of both inputs, indicating that DA and adenosine-mediated suppression of BLA-evoked firing was activity-dependent. These data suggest that increases in mesoaccumbens DA efflux by hippocampal afferents to the NAc play a critical role in an input selection mechanism, which can ensure preferential responding to the information conveyed from the hippocampus to the ventral striatum.

Action Potentials↗

PubMed2001

Changes in dopamine efflux associated with extinction, CS-induced and d-amphetamine-induced reinstatement of drug-seeking behavior by rats.

The present experiment employed chronoamperometry with stearate-graphite paste electrodes to monitor dopamine efflux in the nucleus accumbens during extinction and subsequent reinstatement of bar-pressing for a conditioned stimulus (CS) following presentation of a CS or following a systemic injection of d-amphetamine. Rats self-administered d-amphetamine (0.25 mg/kg per infusion) for 3 h a day on 6 consecutive days. Each infusion was paired with a flashing light CS. On the 7th day, rats self-administered d-amphetamine for 1 h, followed by 10 h of extinction. Presentation of the CS 2 days following extinction induced small and transient increases in responding for the CS, with no significant associated increases in DA efflux. Lower rates of responding were observed in rats that had received random presentations of the CS during d-amphetamine self-administration, and in an experimentally-naïve control group. A subsequent systemic injection of d-amphetamine increased dopamine efflux in the nucleus accumbens in all groups and was most effective in reinstating bar-pressing in the CS-d-amphetamine paired group. This is consistent with the hypothesis that exposure to psychostimulant drugs, and a drug-paired CS, can reinstate drug-seeking behavior. Together, these findings suggest that enhanced DA efflux may contribute to the reinstatement of drug-seeking behavior induced by the single administration of a psychostimulant drug, but not transient reinstatement induced by presentation of a drug-paired CS alone following extinction.

Animals↗

PubMed2000

Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area.

Cholinergic and glutamatergic neurons in the laterodorsal tegmentum (LDT) and neighbouring mesopontine nuclei are thought to influence mesolimbic dopaminergic neuronal activity involved in goal-directed behaviours. We measured the changes in dopamine oxidation current (corresponding with dopamine efflux) in the nucleus accumbens (NAc) in response to electrical stimulation of the LDT using in vivo chronoamperometry in urethane-anaesthetized rats. LDT stimulation (35 Hz pulse trains for 60 s, 1 s intertrain interval) evoked a three-component change in dopamine efflux in the NAc: (i) an initial stimulation time-locked increase in the dopamine signal above baseline, followed by (ii) an immediate decrease below baseline, and thereafter by (iii) a prolonged increase in the dopamine signal above baseline. Intra-VTA infusion of the nicotinic receptor antagonist mecamylamine (5 microg/0.5 microL) or the ionotropic glutamate receptor antagonist kynurenate (10 microg/microL) attenuated the first LDT-elicited component. The second suppressive component was abolished by intra-LDT infusions of either the nonselective or the M2-selective muscarinic receptor antagonists scopolamine (100 microg/microL) and methoctramine (50 microg/microL), respectively. In contrast, intra-VTA infusions of scopolamine (200 microg/microL) resulted in a selective attenuation of the third facilitatory component, whereas both second and third components were abolished by systemic injections of scopolamine (5 mg/kg). These results suggest that the initial increase, subsequent decrease, and final prolonged increase in extracellular dopamine levels in the NAc are selectively mediated by LDT-elicited activation of (i) nicotinic and glutamatergic receptors in the VTA, (ii) muscarinic M2 autoreceptors on LDT cell bodies, and (iii) muscarinic receptors in the VTA, respectively.

Animals↗

PubMed1998

Pre-exposure of rats to amphetamine sensitizes self-administration of this drug under a progressive ratio schedule.

Two groups of male rats were tested to determine whether pre-exposure to d-amphetamine would enhance the motivation to self-administer the drug under a progressive ratio schedule of reinforcement. In the first phase of the experiment, one group of rats received d-amphetamine (2 mg/kg IP), while a second group received saline on alternate days for a total of ten injections. Following a 21-day drug withdrawal period, behavioral sensitization was confirmed by a significant increase in amphetamine-induced stereotypy in the d-amphetamine-pretreated group, relative to the saline-pretreated group. In the second phase of the study, all rats were implanted with chronic jugular catheters and trained to self-administer d-amphetamine (0.2 mg/kg per infusion) under a fixed-ratio schedule of reinforcement. The progressive ratio paradigm was then imposed for 7 consecutive days; d-amphetamine-pretreated rats attained significantly higher break points than saline-pretreated animals. These data suggest that pre-exposure to d-amphetamine may enhance the motivation to self-administer this drug.

Animals↗

PubMed1998

The relation between dopamine oxidation currents in the nucleus accumbens and conditioned increases in motor activity in rats following repeated administration of d-amphetamine or cocaine.

Chronoamperometric recording techniques were used to monitor extracellular dopamine efflux in the nucleus accumbens associated with unconditioned and conditioned increases in motor activity in rats, following the intravenous administration of either d-amphetamine (0.63 mg/kg) or cocaine (3 mg/kg), or the presentation of a conditioned stimulus paired repeatedly with one of these psychostimulants. Each drug was administered daily for 7 days, either in the home cage or an environment in which a compound stimulus (light offset, odour) was presented. Rats in control groups received saline instead of drug in the distinctive test environment. On day 7 of training, significant increases in unconditioned motor activity were observed in the 30 min session following infusions of either d-amphetamine or cocaine. Associated dopamine oxidation currents in the nucleus accumbens increased immediately following administration of either drug and remained significantly elevated above baseline during the entire 30 min recording period. On the test day, presentation of the conditioned stimulus with vehicle infusions, in the distinct environment, was accompanied by an increase in dopamine oxidation currents and a conditioned increase in motor activity, only in the groups in which these stimuli had been paired with d-amphetamine or cocaine. Neither the magnitude or duration of the conditioned motor activity matched the corresponding change in extracellular dopamine efflux in the nucleus accumbens. Accordingly, it is argued that the increase in dopamine concentration serves as a neurochemical correlate of the unconditioned and conditioned stimuli. The change in motor activity constitutes the unconditioned and conditioned responses that are subserved by the neural systems activated by the initial rise in extracellular dopamine.

Animals↗

PubMed1998

Conditioned changes in dopamine oxidation currents in the nucleus accumbens of rats by stimuli paired with self-administration or yoked-administration of d-amphetamine.

In vivo chronoamperometry was used to monitor changes in dopamine oxidation currents corresponding to dopamine efflux in the nucleus accumbens of rats after presentation of a conditioned light stimulus repeatedly paired with either yoked- or self-administered intravenous injections of the psychostimulant d-amphetamine. Daily conditioning trials began with a non-contingent drug injection, paired with a conditioned stimulus consisting of a 5 s flashing light and 30 s lights out, after which a house light was illuminated during the 3 h session, signalling drug availability. Each subsequent injection of d-amphetamine was paired with the conditioned stimulus. Electrochemical measures were taken on conditioning trials 4-7, and on each trial, intravenous d-amphetamine (0.25 mg/kg per injection) self-administration produced a significant maximal increase in mean dopamine oxidation currents of approximately 8 nA above baseline. Dopamine oxidation currents in rats receiving yoked d-amphetamine were approximately 5 nA above baseline by the fourth day of drug administration and reached approximately 8 nA on the seventh and final day of drug administration. On day 9 the first presentation of the vehicle injection and conditioned stimulus, in combination with illumination of the house lights, induced an immediate increase in nucleus accumbens dopamine oxidation currents in all rats that had previously received d-amphetamine. Subsequent presentations of the conditioned stimulus at 30 min intervals induced further increases in extracellular dopamine oxidation currents in both drug-treated groups. By the end of the 3 h session, both groups had similar maximal conditioned increases in dopamine oxidation currents of approximately 6 nA. These data are discussed with relation to the neurochemistry of drug craving.

Animals↗

PubMed1998

Basolateral amygdala stimulation evokes glutamate receptor-dependent dopamine efflux in the nucleus accumbens of the anaesthetized rat.

Afferents from the basolateral amygdala and dopamine projections from the ventral tegmental area to the nucleus accumbens have both been implicated in reward-related processes. The present study used in vivo chronoamperometry with stearate-graphite paste electrodes in urethane-anaesthetized rats to determine how basolateral amygdala efferents to the nucleus accumbens synaptically regulate dopamine efflux. Repetitive-pulse (20 Hz for 10 s) electrical stimulation of the basolateral amygdala evoked a complex pattern of changes in monitored dopamine oxidation currents in the nucleus accumbens related to dopamine efflux. These changes were characterized by an initial increase that was time-locked to stimulation, a secondary decrease below baseline, followed by a prolonged increase in the dopamine signal above baseline. The effects of burst-patterned stimulation (100 Hz, 5 pulses/burst, 1-s interburst interval, 40 s) of the basolateral amygdala on the basal accumbens dopamine signal were similar to those evoked by 20 Hz stimulation, with the lack of a secondary suppressive component. Infusions of the ionotropic glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid (APV) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the nucleus accumbens dose-dependently blocked or attenuated the initial and prolonged increases in the dopamine signal following 20 Hz or burst-patterned basolateral amygdala stimulation. Infusions of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine selectively blocked the intermediate suppressive effect of 20 Hz basolateral amygdala stimulation on dopamine oxidation currents. Blockade of glutamate receptors or inhibition of dopamine neuronal activity via infusions of either APV + DNQX, lidocaine or gamma-hydroxybutyric acid, respectively, into the ventral tegmental area did not effect the pattern of changes in the accumbens dopamine signal evoked by basolateral amygdala stimulation. These data suggest that the glutamatergic basolateral amygdala inputs to nucleus accumbens dopamine terminals synaptically facilitate or depress dopamine efflux, and these effects are independent of dopamine neuronal firing activity. Moreover, these results imply that changes in nucleus accumbens dopamine levels following presentation of reward-related stimuli may be mediated, in part, by the basolateral amygdala.

Amygdala↗

PubMed1997

Increased striatal dopamine efflux follows scopolamine administered systemically or to the tegmental pedunculopontine nucleus.

The cholinergic cells of the tegmental pedunculopontine nucleus monosynaptically excite dopaminergic neurons of the substantia nigra. In vivo electrochemical methods were used to monitor dorsal striatal dopamine efflux in awake rats following intraperitoneal scopolamine injections and following the direct application of scopolamine to the tegmental pedunculopontine nucleus. Systemic injections of scopolamine (1.0, 3.0 or 10.0 mg/kg) resulted in dose-related increases in peak striatal dopamine oxidation currents of between 1.1 and 2.0 nA. Increases began within 10-20 min after injection and peaked after 40-90 min. Unilateral microinjections of scopolamine into the tegmental pedunculopontine nucleus (10, 50 or 100 micrograms/0.5 microliter) resulted in dose-related increases in dopamine oxidation currents that peaked 60-90 min postinjection (2.9-5.0 nA). Carbachol (4.0 micrograms/0.5 microliter) injected unilaterally into the tegmental pedunculopontine nucleus 20 min before 100 micrograms tegmental pedunculopontine nucleus scopolamine, or injected bilaterally 20 min before 3.0 mg/kg systemic scopolamine, attenuated the increases produced by scopolamine alone. The carbachol preinjection tests suggest that the effects of both systemic and tegmental pedunculopontine nucleus scopolamine treatments are mediated largely by muscarinic receptors near the tegmental pedunculopontine nucleus. These findings are consistent with the proposal that enhanced activation of substantia nigra dopamine cells results from scopolamine-induced disinhibition of the tegemental pedunculopontine nucleus cholinergic cell group via blockade of their inhibitory autoreceptors.

Animals↗

PubMed1997

Stimulation of the ventral subiculum of the hippocampus evokes glutamate receptor-mediated changes in dopamine efflux in the rat nucleus accumbens.

The effects of electrical stimulation of the ventral subiculum/CA1 region of the hippocampus on changes in dopamine oxidation current (corresponding to dopamine efflux) in the nucleus accumbens were examined using in vivo chronoamperometry with stearate-graphite paste electrodes in urethane-anaesthetized rats. Burst-patterned monophasic pulses (10-100 Hz/burst delivered at 0.8-4 Hz) evoked a three-component change in dopamine efflux in the nucleus accumbens with an initial transient increase in the dopamine signal above baseline, followed by an immediate decrease below baseline, and thereafter by a prolonged increase in the dopamine signal above baseline. 6-Hydroxydopamine lesions of the mesoaccumbens dopamine pathway or transection of the fimbria-fornix blocked all of the evoked changes in the dopamine signal. Both the first and third components of enhanced dopamine efflux were blocked by microinfusion into the nucleus accumbens of the ionotropic glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione and kynurenate. Burst stimulation-evoked decreases in the dopamine signal were abolished following microinfusions into the nucleus accumbens of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine. These results suggest that ventral subiculum/CA1 glutamatergic inputs to the nucleus accumbens may presynaptically modulate dopamine efflux by synaptic activation of both ionotropic and metabotropic glutamate receptors in the nucleus accumbens. These glutamate-dopamine interactions may constitute part of the mechanisms by which hippocampal signals are integrated through selective modulation of dopamine release in the nucleus accumbens in both physiological and pathological conditions.

Animals↗

PubMed1996

Modulation of dopamine efflux in the nucleus accumbens after cholinergic stimulation of the ventral tegmental area in intact, pedunculopontine tegmental nucleus-lesioned, and laterodorsal tegmental nucleus-lesioned rats.

Microinjections of the cholinergic receptor agonist nicotine and the cholinesterase inhibitor neostigmine were made into the ventral tegmental area (VTA) of urethane-anesthetized rats, and dopamine (DA) efflux in the nucleus accumbens was measured using in vivo chronoamperometry. Dose-dependent increases in the chronoamperometric signals corresponding to increased DA efflux were observed in the nucleus accumbens of normal intact rats after cholinergic stimulation of the VTA. The source of the cholinergic input to the VTA was investigated by making excitotoxic lesions in either the laterodorsal tegmental nucleus (LDTg) or the pedunculopontine tegmental nucleus (PPTg). Compared with sham-operated control animals, which showed the same response as intact, nonlesioned rats, ibotenate lesions of the LDTg attenuated the stimulatory effects of intra-VTA neostigmine on DA efflux in the nucleus accumbens. In contrast, rats with ibotenate lesions of the PPTg showed normal nucleus accumbens DA eflux after intra-VTA injections of neostigmine. Such lesions in the PPTg attenuate DA efflux in the caudate-putamen stimulated by injections of neostigmine into the substantia nigra pars compacta (SNc). The present data show that cholinergic neurons in the LDTg, but not the PPTg, regulate the activity of DA-containing neurons in the VTA, which complements previous data showing that cholinergic neurons in the PPTg regulate DA-containing neurons in the SNc.

Animals↗

PubMed1996

Schedule-induced polydipsia and the nucleus accumbens: electrochemical measurements of dopamine efflux and effects of excitotoxic lesions in the core.

The efflux of dopamine (DA) in the nucleus accumbens (NAcc) core during the acquisition of schedule-induced polydipsia (drinking in response to intermittent food presentation) was measured using rapid scan voltammetry. DA efflux increased throughout the SIP sessions, always reaching a peak after the session had terminated. There was, however, no relationship between the acquisition of the drinking response to intermittent food presentation and DA efflux. When water was absent from the test chamber, DA efflux still increased and reached a peak after food delivery was terminated, dissociating drinking and increased DA efflux. Taken in conjunction with previously presented data, these results suggest that the presence of DA in the NAcc core might be necessary for the development of SIP but that its efflux does not bear a systematic relationship to the acquisition of adjunctive behaviour. In a second experiment the effects of NMDA-induced lesions of the NAcc core on the acquisition and performance of SIP were examined. Lesioned rats did not differ to controls in terms of water intake, mean drinking bout length, latency to panel press for food or to begin drinking. The number of drinking bouts/min was reduced in lesioned rats, but did not reach statistical significance; the number of panel presses/min was significantly reduced in lesioned rats. These data demonstrate that the NAcc core is not necessary for the development of SIP but that elements of performance are affected. This suggests that the development of SIP can be fractionated and that different neural elements control different aspects of its expression. These data are used to support the hypothesis that the NAcc core is involved in focusing behaviour and regulating switching between response options.

Animals↗

PubMed1996

Does monoamine oxidase inhibition by pargyline increase extracellular dopamine concentrations in the striatum?

The present study examined the possibility that pargyline-induced stimulation of dopamine neurotransmission in the striatum measured by intracerebral microdialysis may be related to alterations in the function of dopamine nerve terminals in close proximity to the implanted microdialysis probe. Changes in extracellular concentrations of dopamine were determined bilaterally in the striata of awake rats by microdialysis with concentric dialysis probes and by chronoamperometry with electrochemical (stearate-graphite paste) recording electrodes, after inhibition of monoamine oxidase by pargyline and subsequent blockade of dopamine uptake by nomifensine. Pargyline (75 mg/kg, i.p.) increased dopamine overflow by 14 nM from a mean basal value of 9 nM as determined from dialysis probes implanted in the right striatum. Pargyline failed, however, to increase basal concentrations of dopamine measured by electrochemical electrodes implanted alone in the contralateral striatum. In contrast, 3 h following pargyline, administration of nomifensine (10 mg/kg, i.p.) increased extracellular dopamine concentrations to a similar magnitude above baseline levels in both right and left striata (135 and 127 nM, respectively). In a separate group of rats, electrochemical electrodes were implanted in the left striatum with the tip of the electrode placed directly adjacent to the lumen of a dialysis probe. In contrast to pargyline's inability to increase basal extracellular dopamine measured at individually implanted electrochemical electrodes in the striatum, pargyline administration increased dopamine concentrations measured at electrodes implanted adjacent to non-perfused dialysis probes to an extent similar to that observed by dialysis alone (25 vs 14 nM, respectively). The present study indicates that pargyline increases dopamine concentrations in the region of striatal tissue immediately adjacent to the shaft of a permanently implanted dialysis probe, but not at the tip of an electrochemical electrode. The former effect appears to reflect an interaction between monoamine oxidase inhibition and the effects elicited by the physical presence of the dialysis probe in tissue.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

Improved electrochemical properties of stearate-graphite paste electrodes after albumin and phospholipid treatments.

Stearate-graphite paste electrodes (SGEs) exhibit enhanced dopamine sensitivity and insensivity to asorbic acid electrocatalytic effects in vitro following exposure to unidentified contituents of rat brain tissue homogenates. The present study utilized voltammetry and chronamperometry to compare the electrochemical characteristics of brain-treated SGEs to those treated with potential brain constituent candidates (albumin proteins and phospholipids). Albumin treatments markedly attenuated interference from ascorbate catalytic effects whereas lipids enhanced both electrode capacitance and sensitivity to dopamine. Combined treatments resulted in electrochemical properties that were similar to brain-treated SGEs. Potential mechanisms by which albumin may attenuate ascorbate electrocatalysis of dopamine were investigated using high performance liquid chromatography, with electrochemical detection. The reduction in ascorbate electrocatalytic effects at albumin-treated SGEs may be due to nucleophilic binding of dopamine oxidation products to albumin attached to the electrode surface. Therefore, the unambiguous detection of dopamine by SGEs in vivo may be related to interactions with factors in brain having similar surface-modifying properties.

Animals↗