[show abstract][hide abstract] ABSTRACT: This study explored the behavioural, neurochemical and molecular effects of Delta9-tetrahydrocannabinol (Delta9-THC) and WIN55,212-2, in two rat phenotypes, distinguished on the basis of their vertical activity upon exposure to a novel environment, as high responders (HR) and low responders (LR). Motor effects were assessed under habituated vs. non-habituated conditions. Dopaminergic activity and DARPP-32 phosphorylation were measured in the dorsal striatum, nucleus accumbens, prefrontal cortex and amygdala. These cannabinoids influenced motor activity in a biphasic manner, i.e. low doses stimulated, whereas high doses suppressed motor activity. Dopamine (DA) biosynthesis was increased in most brain regions studied following Delta9-THC administration mainly in HR rats, and low-dose WIN55,212-2 increased DA biosynthesis in HR rats only. Both high and low doses of Delta9-THC increased DARPP-32 phosphorylation in most brain regions studied in both phenotypes, an effect that was also observed following high-dose WIN55,212-2 administration only in the striatum. The present results provide further support for a key role of cannabinoids in the regulation of motoric responses and elements of dopaminergic neurotransmission and reveal their complex differential effects in distinct rat phenotypes, as seen with other drugs of abuse.
The International Journal of Neuropsychopharmacology 11/2009; 13(9):1175-91. · 5.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: Somatostatin infusion in rat ventral pallidum (VP) led to the attenuation of locomotor activity (Marazioti, A., Kastellakis, A., Antoniou, K., Papasava, D., Thermos, K., 2005. Somatostatin receptors in the ventral pallidum/substantia innominata modulate rat locomotor activity. Psychopharmacology 181, 319-326). In the present study, we investigated the putative circuitry involved in somatostatin's actions by examining the involvement of GABAergic neurotransmission in locomotor activity subsequent to somatostatin's infusion into the VP. Male Sprague-Dawley rats, 300-350 g, were used for all experiments. Saline or somatostatin (240 ng/0.5 microl/side) in the absence or presence of bicuculline (GABA-A antagonist; 5 mg/kg/ml, i.p.; 120 ng/side nucleus accumbens (NAc)) or phaclofen (GABA-B antagonist; 10 mg/kg/ml, i.p.; 120 ng/side NAc) were infused bilaterally, and the locomotor activity measured for 60 min using a rectangular activity cage. Somatostatin infused in the VP decreased the locomotor activity of the rat in a statistically significant manner. Bicuculline (i.p., and in the NAc) and phaclofen (only i.p.) reversed SRIF's actions, when administered prior to somatostatin's infusion in the VP. The present study provides further information on somatostatin's involvement in the VP-NAc circuitry, and implicates the GABAergic system in somatostatin's actions in the VP.
[show abstract][hide abstract] ABSTRACT: This study investigated how the administration (acute and chronic) of the antidepressants citalopram and desmethylimipramine (DMI) influences somatostatin (somatotropin release inhibitory factor, SRIF) levels and SRIF receptor density (sst(1-5)) in rat brain. Animals received either of the following treatments: (1) saline for 21 days (control group), (2) saline for 20 days and citalopram or DMI for 1 day (citalopram or DMI acute groups), (3) citalopram or DMI for 21 days (citalopram or DMI chronic groups). Somatostatin levels were determined by radioimmunoassay. [(125)I]LTT SRIF-28 binding in the absence (labeling of sst(1-5)) or presence of 3 nM MK678 (labeling of sst(1/4)) and [(125)I]Tyr(3) octreotide (labeling of sst(2/5)) binding with subsequent autoradiography was performed in brains of rats treated with both antidepressants. Somatostatin levels were increased after citalopram, but not DMI administration, in the caudate-putamen, hippocampus, nucleus accumbens, and prefrontal cortex. Autoradiography studies illustrated a significant decrease in receptor density in the superficial and deep layers of frontal cortex (sst(2)), as well as a significant increase in the CA1 (sst(1/4)) hippocampal field in brains of chronically citalopram-treated animals. DMI administration increased sst(1/4) receptors levels in the CA1 hippocampal region. These results suggest that citalopram and to a lesser extent DMI influence the function of the somatostatin system in brain regions involved in the emotional, motivational, and cognitive aspects of behavior.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2008; 34(4):952-63. · 6.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: Somatostatin and its receptors have been localized in brain nuclei implicated in motor control, such as the striatum, nucleus accumbens, ventral pallidum, and globus pallidus (GP).
The objective of this study was to investigate the role of somatostatin receptors (sst(1,2,4)) in the GP on dopamine (DA)-mediated behaviors, such as locomotor activity, and to examine the GP-striatum circuitry by correlating the effect of somatostatin in the GP with the release of DA in the striatum.
Animals received saline, somatostatin (60, 120, 240 ng/0.5 microl per side) or the following selective ligands: L-797,591 (sst(1) analog, 60, 120, 240 ng/0.5 microl per side), L-779,976 (sst(2) analog, 120, 240, 480 ng/0.5 microl per side), L-803,087 (sst(4) analog; 120, 240, 480 ng/0.5 microl per side), L-796,778 (sst(3) analog, 240 ng/0.5 microl per side), SRA-880 (sst(1) selective antagonist + somatostatin, 120 ng/0.5 microl per side), CYN154806 (sst(2) selective antagonist + somatostatin, 120 ng/0.5 microl per side) bilaterally in the GP of the rat. Locomotor activity was measured for 60 min. The effect of somatostatin, administered intrapallidally, on the extracellular concentrations of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the striatum was also studied in the behaving rat using in vivo microdialysis methodology.
Somatostatin increased the locomotor activity of the rat in a dose-dependent manner. This effect was mediated by activation of the sst(1), sst(2), and sst(4) receptors. Selective sst agonists increased locomotor activity in a statistical significant manner, while selective sst(1) and sst(2) antagonists reversed the somatostatin-mediated locomotor activity to control levels. DA levels increased in the striatum after intrapallidal infusion of somatostatin (240 ng/side).
These data provide behavioral and neurochemical evidence of the functional role of somatostatin receptors in the GP-striatum circuitry.
[show abstract][hide abstract] ABSTRACT: Experimental animals can be differentiated on the basis of their horizontal or vertical activity to high responders (HR) and low responders (LR) upon exposure to a novel environment. These individual differences have been associated with behavioral and neurobiological differences in a number of experimental procedures used for studying sensitivity to psychostimulants, anxiety, depression, and cognitive function. In the present study, we differentiated the rats to HR and LR based on their vertical activity upon exposure to a novel environment. Additionally, we ascertained whether HR and LR rats differ in a battery of tests such as passive avoidance (PA), object recognition (OR), and the water-maze (WM) that provide indices for cognitive function and the forced swim test (FST), an animal model of affective responsivity and antidepressant-like activity. Potential differences in neurochemical indices between the two phenotypes were also examined. HR rats displayed impaired non-spatial object recognition memory, but enhanced spatial performance, as compared to LR rats. FST induced "depressive-like" symptoms in both phenotypes that were differently manifested in HR versus LR rats. Neurochemical findings revealed distinct differences in serotonergic and dopaminergic activity in the striatum and the prefrontal cortex of HR as compared to LR rats. The above results show that HR and LR rats exhibit important differences in a battery of tests related to cognitive performance or affective responsivity, which may be associated with differences in certain neurobiological parameters.
Behavioural Brain Research 04/2008; 187(2):462-72. · 3.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study investigated the in vivo neuronal release of somatostatin in the rat nucleus accumbens (NAc), and the effect of chronic administration of antidepressants. Microdialysis studies were performed on male Sprague-Dawley rats, in accordance with the EU guidelines (EEC Council 86/609). Somatostatin levels were quantified by radioimmunoassay (RIA) or enzyme linked immuno sorbent assay (ELISA). A high concentration of potassium ions (K(+), 100 mM) was used to ascertain the neuronal release of somatostatin. Antidepressant treatments involved the administration of citalopram (20 mg/2 ml/kg, i.p., once daily) or desipramine (DMI, 5 mg/2 ml/kg, i.p., twice daily) for 21 days. Control groups received saline (2 ml/kg for 21 days, i.p.) once or twice daily respective of the antidepressant treatment. Basal levels of somatostatin released were found to be 20.01+/-0.52 fmol/sample. K(+) (100 mM) increased somatostatin levels at 205% of basal. Chronic citalopram and desipramine treatments also increased the somatostatin levels by 83+/-32% and 40+/-6% of basal, respectively. These findings indicate that somatostatin is released neuronally in the NAc. Antidepressants influence its release in a positive manner, suggesting the necessity of further studies for the elucidation of the involvement of somatostatin in the putative therapeutic effects of these agents.
[show abstract][hide abstract] ABSTRACT: Newly developed cannabinoids may hold the promise of the development of useful and safe drugs. This study aimed to investigate the behavioral effects of the novel 1',1'-dithiolane delta8-HC analogue AMG-3, a cannabinomimetic molecule with high affinity for CB1/CB2 receptors. This analog was chosen for its binding affinity to these receptors, which is higher than that reported for delta8-tetrahydrocannabinol (delta8-THC). Behavioral responses were assessed after the administration of AMG-3 (1, 2, 4, 8 mg/kg, i.p.) in the open field, on the bar test, on the hot plate and in the intracranial self-stimulation procedure. AMG-3 increased the reactivity time on the hot plate in a dose- and time-dependent manner, indicating a long-lasting analgesic effect (at least 24 h). The substance was found dose-dependently to decrease spontaneous motor activity and to induce catalepsy, particularly at the highest dose (8 mg/kg). AMG-3 did not affect the rewarding value of intracranial self-stimulation, except to increase the reward threshold at the highest dose (8 mg/kg). The effects of the highest dose of AMG-3 on spontaneous activity and on the self-stimulation paradigm were completely reversed by pre-treatment with the CB1 receptor antagonist AM-251. These findings indicate that the administration of AMG-3 to rats elicits a specific behavioral profile, most probably associated with the activation of CB1 receptors and without effects indicating abuse potential.
[show abstract][hide abstract] ABSTRACT: Dopamine and somatostatin have been implicated in the pathophysiology of depression. We have employed in vivo microdialysis to investigate the regulation of dopamine release by somatostatin in the nucleus accumbens and the striatum of awake, freely moving rats, and to ascertain how this regulation may be affected by desipramine treatment. Somatostatin-14 (10(-4) M) infusion induced an increase in the release of dopamine and a decrease in the release of its metabolites in both the nucleus accumbens (568% of basal) and the striatum (546% of basal). Chronic desipramine treatment resulted in an exaggerated somatostatin-induced increase of dopamine levels, specifically in the nucleus accumbens (3542% compared with 564% of basal in the striatum), whereas acute desipramine treatment had no effect (582% of basal) compared with saline treated rats. Basal concentrations of dopamine and metabolites were not influenced by either chronic or acute treatment of desipramine in either brain area. These results demonstrate that somatostatin regulates dopamine release in the nucleus accumbens and the striatum. Chronic antidepressant treatment influences somatostatin's actions on dopamine function selectively in the nucleus accumbens.
European Journal of Neuroscience 09/2001; 14(4):763-7. · 3.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been shown that nicotine facilitates intracranial self-stimulation (ICSS) reward and that nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA) are of primary importance for its reinforcing and dependence-producing actions. Recently, we have shown that alpha 7 nicotinic receptors in the VTA contribute to both the acute effects of nicotine on the mesolimbic dopamine system, as well as to nicotine withdrawal reactions. However, it is not yet known whether the same receptor conformation is directly involved in the reinforcing actions of nicotine. Here, using the curve-shift method we studied the effects of methyllycaconitine (MLA), a selective alpha 7 receptor antagonist, microinjected (graded doses: 1, 3, 9 micrograms/microliter per side) into the VTA on the rewarding efficacy of lateral hypothalamic self-stimulation and on the systemic nicotine-induced potentiation of brain stimulation reward. MLA did not affect baseline self-stimulation. Nicotine produced a significant reduction in ICSS threshold, without altering maximal rates of responding, while MLA attenuated the effect of nicotine at the two lower doses. Given the reported interaction between nicotine and cocaine at both the neuronal and the behavioral level, we also examined whether alpha 7 receptor antagonism within the VTA can affect the reinforcing action of cocaine, as measured with ICSS. Interestingly, MLA attenuated the reinforcing effect of cocaine in all doses tested, without altering the maximal rate of responding, i.e. the performance of the animals. These results suggest that alpha 7 nAChRs in the VTA are involved in mediating the reinforcing actions of drugs of abuse, such as nicotine and cocaine, and provide evidence that alpha 7 nAChR antagonists may be clinically useful in attenuating the rewarding effects of addictive drugs.
[show abstract][hide abstract] ABSTRACT: Exposure to an environment, previously conditioned to amphetamine (1 mg/kg, i.p.), induced locomotor activity and c-fos expression (a marker for neuronal activation) in the mouse medial prefrontal cortex (mPFC) and amygdala; acute or repeated amphetamine (1 mg/kg, i.p.) administration induced c-fos expression additionally in the nucleus accumbens. An alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-receptor antagonist, 2, 3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)quinoxaline (NBQX), blocked expression of conditioned activity, and prevented the increase in c-fos expression in mPFC, implicating mPFC AMPAergic transmission in the conditioned component of behavioural sensitization to amphetamine. NBQX failed to block the expression of amphetamine-conditioned place preference, a measure of conditioned reward, or conditioned c-fos expression in the amygdala, an area implicated in the expression of conditioned place preference. These findings indicate that the conditioned components of behavioural sensitization depend on AMPA-receptor-mediated activation in mPFC, but that conditioned reward does not.
European Journal of Neuroscience 12/1999; 11(11):4089-98. · 3.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: Exposure to an environment, previously conditioned to amphetamine (1 mg/kg, i.p.), induced locomotor activity and c-fos expression (a marker for neuronal activation) in the mouse medial prefrontal cortex (mPFC) and amygdala; acute or repeated amphetamine (1 mg/kg, i.p.) administration induced c-fos expression additionally in the nucleus accumbens. An -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)quinoxaline (NBQX), blocked expression of conditioned activity, and prevented the increase in c-fos expression in mPFC, implicating mPFC AMPAergic transmission in the conditioned component of behavioural sensitization to amphetamine. NBQX failed to block the expression of amphetamine-conditioned place preference, a measure of conditioned reward, or conditioned c-fos expression in the amygdala, an area implicated in the expression of conditioned place preference. These findings indicate that the conditioned components of behavioural sensitization depend on AMPA-receptor-mediated activation in mPFC, but that conditioned reward does not.
European Journal of Neuroscience 10/1999; 11(11):4089 - 4098. · 3.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: Enkephalinergic and dopaminergic mechanisms have been implicated in the electrical self-stimulation (SS) behavior. The present set of experiments investigated the role of opioid receptors within DA-innervated brain regions (nucleus accumbens and ventral tegmental area) in the ventral pallidum self-stimulation (VP-SS). Forty-one rats used in this study were implanted with a monopolar moveable stimulating electrode in the VP. A rate-frequency curve-shift method was applied to determine the reward (threshold) and motor functions (asymptotic rate) of self stimulation elicited from the VP. One group received systemic treatment of graded doses (vehicle; 1.25; 2.50 mg/kg) of morphine injected IP, 60 min before behavioural testing. The results showed a tendency for increased threshold of VP-SS and of the asymptotic rate of responding. Three additional groups were implanted with guide cannulae in the nucleus accumbens (NAC), the ventral tegmental area (VTA) or dorsally to the VTA and received microinjections of morphine (vehicle: 1.25; 2.50; 5.0; 10.0 microg/0.5 microl per side). Central injections of morphine higher than 1.25 microg/side into the VTA were associated with a significant reduction in VP-SS thresholds, indicating a potentiative effect on reward. Microinjections of morphine either into the NAC or into the dorsal tegmentum did not produce significant alterations on thresholds or responding of VP-SS. In order to investigate the extent to which the VTA-NAC dopamine projection was involved in the SS behavior elicited from the ventral pallidum, we tested SS in animals that suffered NAC 6-hydroxydopamine (6-OHDA) lesions. Rats suffering NAC dopamine depletion along with their corresponding controls showed similar levels of thresholds and responding to the ones exhibited prior to the lesion, revealing that NAC dopamine is not necessary to maintain VP-SS. The results suggest that stimulation of opioid receptor in the VTA increases the rewarding efficacy of VP-SS. This effect might be due to the modulation of VTA-DA neurons projecting to the VP rather than to the NAC.
[show abstract][hide abstract] ABSTRACT: It has been hypothesized that the intrapallidal morphine-induced dopamine release in the nucleus accumbens may be mediated by thalamocorticostriatal or mesolimbic pathways. In order to challenge the above hypothesis, we examined whether changes in accumbal dopamine and its metabolites produced by intrapallidal morphine a) are associated with local excitatory amino acid neurotransmission b) are determined by impulse propagation in dopamine neurons and c) are observed both ipsi- and contralateral to the morphine administration site. In vivo microdialysis was used to assess dopamine release and metabolism in the right and the left nucleus accumbens separately of awake, unrestrained rats. Vehicle or morphine hydrochloride (10 microliters/26.0 mM) was applied unilaterally into the pallidum alone or in combination with ipsilateral application of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) into the nucleus accumbens or the sodium channel blocker tetrodotoxin into the medial forebrain bundle. Drugs' application was performed via reverse dialysis. Concentrations of dopamine, 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the collected dialysate were measured by high performance liquid chromatography with electrochemical detection. Morphine administration resulted in elevated levels of dopamine in the ipsilateral and of DOPAC and HVA in both the ipsi- and contralateral nucleus accumbens. Dizocilpine (MK-801) (0.3 mM) did not influence the basal levels of dopamine, DOPAC or HVA in the nucleus accumbens. Ipsilaterally, dizocilpine (MK-801) inhibited the effect of morphine on dopamine release, whereas it increased significantly the effect of the drug on DOPAC and HVA. Tetrodotoxin (3 microM) reversed the effect of intrapallidal morphine on dopamine, DOPAC or HVA in the ipsilateral nucleus accumbens. The results show that the intrapallidal morphine-induced dopaminergic activation in the ipsilateral nucleus accumbens is dependent upon both phasic and tonic activation of dopaminergic neurons. They suggest that both the thalamocorticostriatal and the mesolimbic dopamine pathways may mediate the investigated effect of morphine.
European Neuropsychopharmacology 03/1998; 8(1):47-53. · 4.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: Neuronal expression of Fos, the protein product of the immediate early gene c-fos has been used as a high resolution metabolic marker for mapping polysynaptic pathways in the brain. We used Fos immunohistochemistry to reveal neuronal activation following self-stimulation of the ventral pallidum. Four groups of rats were allowed to self-stimulate for 30 min with 0.4 s trains of cathodal rectangular pulses of constant intensity (0.4 mA) and duration (0.1 ms). Each group was assigned a different pulse frequency, (3, 17, 24 and 50 pulses/stimulation train). Which was preselected from within each animal's rate-frequency function. The subjects that were assigned three pulses failed to self-stimulate and were considered as controls. The subjects that were assigned 17 pulses self-stimulated at half-maximal rate, whereas those that were assigned 24 and 50 pulses self-stimulated at maximal rates. The animals were sacrificed 90 min after the self-stimulation session and their brains were processed for Fos-like immunoreactivity. Fos-like immunoreactivity was found to increase as a function of pulse frequency in several brain regions known to be involved in drug and/or brain stimulation reward (medial prefrontal cortex, lateral septum, nucleus accumbens; lateral hypothalamus and ventral tegmental area), whereas it was not affected in structures devoid of such involvement (substantia nigra reticulata and dorsolateral striatum). The level of Fos expression induced by trains of 50 pulses was considerably higher than that produced by 24 pulses although both frequencies supported the same (maximal) self-stimulation rate. This finding indicates that Fos expression correlated with reward magnitude (known to increase between these frequencies), not with bar-pressing rate, thus suggesting the presence of a reward-specific effect. The finding of a frequency-dependent Fos expression in a behavioural paradigm can be considered analogous to a pharmacological dose-response curve and, as such, our results may open new avenues for the use of Fos immunohistochemistry in quantitative neurobehavioural studies.
[show abstract][hide abstract] ABSTRACT: Dopamine-somatostatin interactions were investigated in the rat striatum using in vivo microdialysis. Somatostatin-14 and somatostatin-28 (10(-4), 10(-5), 10(-6) M) were infused, and the levels of dopamine and its metabolites DOPAC and HVA were assessed using high pressure liquid chromatography with electrochemical detection. Somatostatin-14 was more effective than somatostatin-28 in producing a dose-dependent increase in dopamine levels with no significant alterations in the levels of the metabolites. To assess the effect of dopamine on somatostatinergic neurons, dopaminergic agents were administered and somatostatin levels measured using a radioimmunoassay. The nonselective agonist apomorphine was administered subcutaneously (0.00, 0.05, 0.10, 0.50, 1.00 mg/kg) or directly infused (10(-4), 10(-5) M) in the striatum. The selective D1 and D2 dopamine antagonists SCH23390 and sulpiride, respectively, were also infused at concentrations of 10(-4) and 10(-5) M. None of these agents elicited any significant changes in the somatostatin release in the striatum, while altering dopamine release. This study provides for the first time evidence regarding dopamine-somatostatin interactions in the awake and freely moving animal. The results confirm that somatostatin modulates the function of dopaminergic neurons in the striatum and provide new evidence that somatostatin-14 may differentially regulate dopamine release. Furthermore, our findings suggest that dopamine does not play a major role in the regulation of somatostatin neurons.
[show abstract][hide abstract] ABSTRACT: The present study examines the role of dopaminergic neurotransmission in modulating the reinforcing effect of ventral pallidum (VP) intracranial self-stimulation (ICSS). Fifty four adult rats were implanted with a monopolar moveable stimulating electrode in the VP. Rate-frequency functions were determined by logarithmically decreasing the number of pulses in a stimulation train from a value that sustained maximal responding to one that did not sustain responding. After the ICSS thresholds stabilized, the animals received treatments with several doses of cocaine and of various selective drugs acting at the level of DA receptor subtypes. Their effects on threshold and asymptotic rate were analyzed. Cocaine produced a significant decrease in ICSS threshold but had no significant effect on the asymptotic rate. A significant decrease in ICSS threshold was also seen with the D3 agonist 7-OH-DPAT. This was associated with a decrease rather than an increase in performance. D1 and D2 DA receptor blockers (haloperidol, SCH-23390, raclopride and sulpiride) produced a dose dependent increase in ICSS threshold and a decrease in the maximal rate. The results suggest that DA plays a modulatory role in VP intracranial self-stimulation, and that D1, D2 and D3 receptors are involved in the mediation of this effect, although to different extents.
[show abstract][hide abstract] ABSTRACT: The degree of neural recovery from refractoriness was inferred in rats self-stimulating with pairs of pulses in the ventral pallidum. The prerecovery intrapair interval varied from 0.5 to 1.0 ms, depending on brain site. At some sites, recovery reached its maximum within less than 1.6 ms whereas, at the majority of sites, a substantial amount of recovery occurred at delays longer than 1.2 ms. The shortest recovery estimates were not fundamentally different from those obtained from sites lying along the medial forebrain bundle. The longest recovery estimates were similar to those obtained from cortical and basal forebrain sites. The differences in recovery noted between sites and the presence of step-like patterns in the recovery curves suggest the presence of neural heterogeneity within the ventral pallidal substrates of reward.
[show abstract][hide abstract] ABSTRACT: The distribution of electrical self-stimulation (ESS) foci within the ventral pallidum (VP) was mapped using moveable electrodes in rats. The function relating ESS bar-pressing rate to the frequency of cathodal rectangular pulses (0.4 mA and 0.1 ms) was obtained for several positions of a moveable electrode in the VP and in the various adjacent to VP nuclei. The rate-frequency functions were fitted to a sigmoid model to obtain the asymptotic rate and threshold frequency. ESS was found in almost all (98%) VP sites tested and to a lesser degree (66%) in the surrounding areas (namely globus pallidus and caudate). Depending on the VP site, maximum rates varied from 14 to 85 bar presses/min, whereas threshold frequencies varied from 10.2 to 36.4 pulses/train; no correlation between these two aspects of ESS was found. Extra-pallidal areas contained less low-frequency threshold sites compared to VP. The lowest threshold found in the VP was slightly higher than that usually obtained for the most rewarding brain areas (VTA, dorsal raphé, LH, amygdala), which suggests that the VP represents an important structure for reward. Furthermore the threshold frequencies were found to decline along the rostrocaudal axis of the VP which supports the view that the VP is heterogeneous in regard to reward related functions.
Behavioural Brain Research 07/1995; 68(2):165-72. · 3.33 Impact Factor