Reduced accumbens dopamine in Sprague-Dawley rats prone to overeating a fat-rich diet

Obese humans and animals exhibit reduced functioning of the dopamine (DA) system in the nucleus accumbens (NAc). The question addressed here is whether this change in NAc DA can be detected in Sprague-Dawley rats that are prone to obesity on a fat-rich diet but still at normal body weight. Rats were subgrouped as “obesity-prone” (OP) or “obesity-resistant” (OR), based on their weight gain during 5 days of access to a high-fat diet, and were then shifted to a lower-fat chow diet before microdialysis testing was performed. The OP rats compared to OR rats exhibited markedly reduced basal levels of DA in the NAc. After a high-fat challenge meal, both OP and OR rats showed a significant increase in extracellular DA and its metabolites; however, the NAc DA of the OP rats still remained at reduced levels. Also, the increase in DA and metabolite levels observed in OR rats after systemic administration of a fat emulsion was not evident in the OP rats, which instead showed no change in DA and a decrease in its metabolites. These results demonstrate, first, that fat can stimulate accumbal DA release and, second, that outbred rats prone to overeating and becoming obese on a palatable, fat-rich diet exhibit reduced signaling in the mesolimbic DA system while still at normal weight, suggesting that it may be causally related to their excess consummatory behavior.     

Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry

The present studies investigated sexual dimorphisms in dopamine release and uptake using fast-scan cyclic voltammetry in anesthetized rats and in brain slices. Electrical stimulation of the medial forebrain bundle of anesthetized rats at high frequency (60 Hz) elicited significantly more extracellular dopamine in the caudate nucleus of females than males. This sex difference was apparent over a range of current intensities applied to the stimulating electrode. Local electrical stimulation of brain slices in vitro verified in vivo results as more extracellular dopamine was elicited by single and 10 pulse stimulations in the caudate nucleus of females. Kinetic analysis of in vivo and in vitro dopamine overflow data indicated that dopamine release (the concentration of dopamine released per stimulus pulse) and the maximal velocity of dopamine uptake are greater in female rats, but the affinity of the transporter for dopamine was the same in males and females. None of these three parameters varied across the female estrous cycle. Linear regression analysis of dopamine release versus maximal uptake velocity data indicated a significant association of release and uptake sites in each sex and regression lines for males and females virtually overlapped.One explanation for these results is greater dopamine neuron terminal density in female caudate nucleus. These sexual dimorphisms in dopaminergic neurotransmission provide a novel, plausible mechanism to explain robust sex differences in behavioral responses of rats to pyschostimulant drugs and may have implications for human neurological disorders and drug abuse.     

An intact dopaminergic system is required for context-conditioned release of 5-HT in the nucleus accumbens of postweaning isolation-reared rats

We investigated the effect of the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (AMPT) on extracellular dopamine and 5-HT levels in the nucleus accumbens of group- and isolation-reared rats. Microdialysis with high-performance liquid chromatography-electrochemical detection was used to quantify dopamine and 5-HT efflux in the nucleus accumbens following foot shock and in association with a conditioned emotional response (CER). Isolation- and group-reared rats received i.p. injections of either saline (0.9%) or AMPT (200 mg/kg) 15 h and 2 h prior to sampling. There was no significant difference between saline-treated isolation- or group-reared rats for basal efflux of dopamine or 5-HT, however as expected, AMPT-treatment significantly reduced dopamine efflux in both groups to an equivalent level (50-55% saline-treated controls). Exposure to mild foot shock stimulated basal dopamine efflux in saline-treated groups only, although the effect was significantly greater in isolation-reared rats. In AMPT-treated rats, foot shock did not affect basal dopamine efflux in either rearing group. Foot shock evoked a prolonged increase in 5-HT efflux in both isolation- and group-reared saline-treated rats but had no effect on 5-HT efflux in AMPT-treated rats. In response to CER, isolation-rearing was associated with significantly greater efflux of both dopamine and 5-HT in saline-treated rats, compared to saline-treated, group-reared controls. However in AMPT-treated rats, efflux of dopamine or 5-HT did not change in response to CER. These data suggest that unconditioned or conditioned stress-induced changes in 5-HT release of the nucleus accumbens are dependent upon intact catecholaminergic neurotransmission. Furthermore, as the contribution of noradrenaline to catecholamine efflux in the nucleus accumbens is relatively minor compared to dopamine, our findings suggest that dopamine efflux in the nucleus accumbens is important for the local regulation of 5-HT release in this region. Finally, these findings implicate the isolation-enhanced presynaptic dopamine function in the accumbens with the augmented ventral striatal 5-HT neurotransmission characterized by isolation-reared rats.     

Effect of nitric oxide synthase inhibitor and NMDA receptor antagonist on the development of nicotine sensitization of nucleus accumbens dopamine release: An in vivo microdialysis study

We have previously found that the neuronal nitric oxide synthase inhibitor N-nitro-l-arginine (l-NNA) and the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 prevent behavioral sensitization to nicotine. This study aimed to investigate the effect of l-NNA and MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drugs on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague–Dawley rats were pretreated with l-NNA (15 mg/kg, i.p.), MK-801 (0.3 mg/kg, i.p.), or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for seven consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens for 60 min and DA release was monitored using in vivo microdialysis. In rats treated with repeated nicotine, acute nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response = 969 ± 235% (mean ± S.E.M.) of basal level versus 520 ± 93%, p = 0.042). Co-administration of l-NNA or MK-801 with nicotine attenuated an increase of DA release elicited by acute nicotine challenge, compared with nicotine alone (maximal DA response = 293 ± 58% and 445 ± 90% of basal level, respectively versus 969 ± 235%, p = 0.004 and p = 0.013, respectively). These data demonstrate that l-NNA and MK-801 block the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of nitric oxide and NMDA receptors in the development of behavioral sensitization to nicotine.     

Neurotensin microinjection into the nucleus accumbens antagonizes dopamine-induced increase in locomotion and rearing

Neurotensin is an endogenous neuropeptide with neuronal perikarya or fibers distributed in the vicinity of the mesolimbic dopamine system. This observation, plus behavioral data showing that neurotensin injection into the nucleus accumbens blocks some behavioral effects of amphetamine, indicates that neurotensin may modulate the mesolimbic dopamine system. In this study it was shown that neurotensin given into the nucleus accumbens produces a dose-dependent blockade of locomotion and rearing initiated by dopamine injection into the nucleus accumbens. This effect is not mimicked by inactive neurotensin analogue nor some other endogenous neuropeptides. Since dopamine acts on postsynaptic dopamine receptors in the nucleus accumbens, neurotensin is acting, not on dopamine terminals, but on neurons or neuronal systems which are modulated by the mesolimbic dopamine system. This conclusion is supported by the facts that intra-accumbens injection of neurotensin does not alter accumbens levels of dopamine or its metabolites, nor does it affect the increase in dopamine metabolites produced by injection of neurotensin into the ventral tegmental area. Further, neurotensin was also found to block the dopamine-independent increase in locomotion and rearing produced by the injection of d-Ala²-Met-⁵enkephalinamide into the nucleus accumbens.These data indicate that neurotensin acts on neurons in the nucleus accumbens to counteract the motor stimulant effects of dopamine or enkephalin. Therefore, in the nucleus accumbens, neurotensin is not acting to modulate the mesolimbic dopamine system, but rather appears to antagonize behavioral hyperactivity, regardless of the neurochemical initiation.     

2-Chloro-N-[(S)-phenyl [(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide, monohydrochloride, an inhibitor of the glycine transporter type 1, increases evoked-dopamine release in the rat nucleus accumbens in vivo via an enhanced glutamatergic neurotransmission

2-Chloro-N-S-phenyl 2S-piperidin-2-yl methyl]-3-trifluoromethyl benzamide, monohydrochloride (SSR504734) is a potent and selective inhibitor of the glycine transporter type 1, which increases central N-methyl-D aspartate glutamatergic tone. Since glutamate has been shown to play a role in the regulation of the dopaminergic system in dopamine-related disorders, such as schizophrenia, we investigated the possibility that SSR504734 may modify the basolateral amygdala-elicited stimulation of dopamine release in the nucleus accumbens via an augmentation of glutamate receptor-mediated neurotransmission. First, our data confirmed that SSR504734 is an inhibitor of GlytT1. In the nucleus accumbens of anesthetized rat, SSR504734 (10 mg/kg, i.p.) induced an increase of extracellular levels of glycine as measured by microdialysis coupled with capillary electrophoresis with laser-induced fluorescence detection. Second, the data demonstrated that SSR504734 (10 mg/kg, i.p.) enhanced the facilitatory influence of glutamatergic afferents on dopamine neurotransmission in the nucleus accumbens. Using an electrochemical technique, we measured dopamine release in the nucleus accumbens evoked by an electrical stimulation of the basolateral amygdala. SSR504734 facilitated dopamine release evoked by a 20 or a 40 Hz frequency basolateral amygdala stimulation. This facilitatory effect was dependent on glutamatergic tone, as intra-nucleus accumbens application of 6-7-dinitroquinoxaline-2,3-dione (10(-3) M) or DL-2-amino-5-phosphonopentanoic acid (10(-3) M), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D aspartate receptors antagonists, respectively, inhibited dopamine release evoked by basolateral amygdala stimulation. Furthermore DL-2-amino-5-phosphonopentanoic acid co-administrated with SSR504734 hampered the dopamine-evoked release facilitation. These data underline the in vivo implication of the glycine uptake mechanism in the control of subcortical glutamate/dopamine interactions.     

Effects of local delta and mu opioid receptor activation on basal and stimulated dopamine release in striatum and nucleus accumbens of rat: an in vivo electrochemical study.

The magnitude and duration of spontaneous and of potassium-stimulated dopamine release were electrochemically measured in striatum and nucleus accumbens of chloral hydrate-anesthetized rats following [D-Pen2-D-Pen5]enkephalin, a delta opioid receptor agonist, or [Tyr-D-Ala-MePhe-Gly-ol], a mu opioid receptor agonist, microinjected directly into the voltammetric recording sites. The data show that delta receptor activation potentiated potassium-stimulated dopamine efflux in striatum and in nucleus accumbens but had no effect on spontaneous dopamine release in either region, whereas mu receptor activation produced unreliable effects in both regions, either having no effect or inhibiting stimulated dopamine efflux without affecting basal levels of extracellular dopamine in either region. The data suggest that some delta opioid receptors in the caudate-putamen and in the nucleus accumbens presynaptically enhance impulse-dependent dopamine release from nigrostriatal and mesolimbic dopamine terminals.     

Peripherally administered ghrelin induces bimodal effects on the mesolimbic dopamine system depending on food-consumptive states

Ghrelin induces orexigenic behavior by activation of growth hormone secretagogue 1 receptors (GHSRs) in the ventral tegmental area (VTA) as well as hypothalamus, suggesting the involvement of mesolimbic dopamine system in the action of ghrelin. The present study aimed to identify neuronal mechanisms by which peripherally administered ghrelin regulates the mesolimbic dopamine system under different food-consumptive states. Ghrelin was administered to rats peripherally (3 nmol, i.v.) as well as locally into the VTA (0.3 nmol). Dopamine in the nucleus accumbens shell (NAc) was measured by microdialysis. Peripheral administration of ghrelin decreased dopamine levels in the NAc when food was removed following ghrelin administration. This inhibitory effect was mediated through GABA_A and N-methyl-d-aspartate (NMDA) receptors in the VTA. In contrast, when animals consumed food following ghrelin administration, dopamine levels increased robustly. This stimulatory effect was mediated through NMDA receptors, but not through GABA_A receptors, in the VTA. Importantly, both the inhibitory and stimulatory effects of ghrelin primarily required activation of GHSRs in the VTA. Furthermore, local injection of ghrelin into the VTA induced dopamine release in the NAc and food consumption, supporting the local action of ghrelin in the VTA. In conclusion, peripherally administered ghrelin activates GHSRs in the VTA, and induces bimodal effects on mesolimbic dopamine neurotransmission depending on food-consumptive states.     

Studies on the influence of nicotine infusions on mesolimbic dopamine and locomotor responses to nicotine

The present study examined the effects of constant nicotine infusions on dopamine overflow in the nucleus accumbens and on locomotor activity and compared them with the changes evoked by repeated daily injections (one injection per day for 5 days) of the drug. The putative anxiolytic properties of nicotine have also been examined using the elevated plus-maze test of anxiety. Repetitive daily subcutaneous injections of nicotine (0.4 mg/kg) enhanced (P < 0.01) the overflow of dopamine evoked by a challenge dose of the drug (0.4 mg/kg) and increased (P < 0.01) its stimulatory effects on locomotor activity. The constant infusion of nicotine, at doses of 1 and 4 mg/kg per day, abolished (P < 0.05) the effects of a bolus injection of nicotine on extracellular dopamine and attenuated (P < 0.01) the enhanced locomotor response evoked by daily pretreatment with nicotine boli. The mesolimbic dopamine response to a bolus injection of nicotine was not significantly attenuated by nicotine infusions when the dose was reduced to 0.25 mg/kg per day. The locomotor responses in these rats were significantly (P < 0.05) less than those seen in the animals pretreated with nicotine injections alone but were also higher (P < 0.05) than those seen in saline-treated control rats given a bolus injection of nicotine. Neither the constant infusion (4 mg/kg per day) nor the injection of nicotine (0.4 mg/kg) evoked an anxiolytic or anxiogenic effect in the elevated plus-maze test. However, the nicotine infusions did abolish the locomotor stimulant effects of the drug in this apparatus. They also abolished the plasma corticosterone response to nicotine and attenuated the plasma corticosterone response to the maze. The data suggest that constant infusions of nicotine, at doses of 1 mg/kg per day or more, may cause desensitisation of the nicotinic receptors which mediate the stimulatory effects of the drug on mesolimbic dopamine release and locomotor activity. The data also suggest that the receptors which mediate the increase in plasma corticosterone, seen in animals given nicotine boli, may also be desensitised by nicotine infusions, and that these receptors may be implicated in the adrenocortical response to anxiogenic stimuli.Abbreviations DA dopamine - NAcc nucleus accumbens Correspondence to: M.E.M. Benwell     

Dietary obesity in adult rats: Similarities to hypothalamic and human obesity syndromes

Normal adult female rats fed a variety of supermarket foods in addition to lab chow rapidly gained weight and became obese compared to rats fed only lab chow. Group housing the animals in an enriched environment did not alter the development of dietary obesity, but housing the rats in activity wheels reduced, although did not prevent, the obesity. The dietary obese rats did not normally defend their excessive weights since they were less willing to eat quinine diets, worked less for food, failed to increase their activity when deprived, and regained their weight at a slower rate following a fast than did controls. The similarity between this behavioral pattern and that displayed by hypothalamic obese rats and overweight humans is discussed.     

Implication of brain-derived neurotrophic factor in the release of dopamine and dopamine-related behaviors induced by methamphetamine

It is widely recognized that methamphetamine enhances the release of dopamine at dopaminergic neuron terminals of the mesolimbic system, which induces dopamine-related behaviors. Brain-derived neurotrophic factor (BDNF), a neurotrophin, binds to and activates its specific receptor tyrosine kinase, TrkB. BDNF has been shown to influence the release of dopamine in the mesolimbic dopamine system. The present study was designed to investigate roles of BDNF and TrkB in the expression of methamphetamine-induced dopamine release in the nucleus accumbens and dopamine-related behaviors induced by methamphetamine in rats. Methamphetamine (1 mg/kg, s.c.) produced a substantial increase in the extracellular levels of dopamine and induced a progressive augmentation of dopamine-related behaviors such as rearing and sniffing. In contrast, both the stimulation of dopamine release and induction of dopamine-related behaviors by methamphetamine were significantly suppressed by pretreatment with intra-nucleus accumbens injection of either BDNF (2.0 microl/rat, 1:1000, 1:300 and 1:100) or TrkB (2.0 microl/rat, 1:1000 and 1:100) antibody. Furthermore, the basal level of dopamine in the nucleus accumbens was not affected by treatment with both BDNF and TrkB antibodies. These findings provide further evidence that BDNF/TrkB pathway is implicated in the methamphetamine-induced release of dopamine and the induction of dopamine-related behaviors.     

Anti-opioid effects of neuropeptide FF receptors in the ventral tegmental area

The present study investigates the modulatory effects of neuropeptide FF (NPFF) receptors on the mesolimbic dopaminergic pathway controlled by opioid receptors. A stable NPFF₂ receptor agonist, dNPA, was injected into the ventral tegmental area (VTA) and the release of dopamine and serotonin within the nucleus accumbens (NAc), induced by intraperitoneal injection of morphine, was monitored using the brain microdialysis, in non-constrained rat. dNPA decreased systemic morphine-induced elevation of dopamine and serotonin metabolites within the NAc. Furthermore, co-injected with morphine into the VTA, NPFF inhibited morphine-induced stereotypy 60–120 min after the injection. This neurochemical and behavioural anti-opioid effect mediated by NPFF₂ receptors at the level of VTA suggests the involvement of NPFF in the rewarding effects of opiates on the mesolimbic dopamine system.     

Effects of neurotensin on dopamine release and metabolism in the rat striatum and nucleus accumbens: cross-validation using in vivo voltammetry and microdialysis

The effects of the neuropeptide neurotensin on dopamine release and metabolism in the posteromedial nucleus accumbens and anterior dorsomedial striatum of the anesthetized rat were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose-dependent augmentation of dopamine efflux as evidenced by increases in the chronoamperometric signal was observed in the nucleus accumbens following intracerebroventricular injections of neurotensin. However, neurotensin failed to alter extracellular concentrations of dopamine in the striatum. The selective effects of neurotensin on mesolimbic dopamine neurons were confirmed using in vivo microdialysis. These results demonstrate that neurotensin can selectively enhance the release and metabolism of dopamine in neurons projecting from the ventral tegmental area to the nucleus accumbens.     

Exercise and the development and persistence of dietary obesity in male and female rats

Adult male and female hooded rats were housed in sedentary conditions or were given free access to a running wheel. Exercising and sedentary rats received either a palatable, mixed, high energy diet with chow (experimental group) or only chow (control group). Exercise reduced the weight gain of the males but not of the females. All experimental groups preferentially selected the palatable foods. Both exercising and sedentary females and the sedentary males became obese compared to their controls, but the exercising males did not. The mixed diet was withdrawn after 10 weeks: thereafter the male and female sedentary experimental groups maintained the elevated body weight. The exercising experimental females showed significant weight loss. Analysis of x-ray photographs indicated that elevated body weight in the experimental rats probably reflected increased deposition of fat and not skeletal growth. The results show that the effect of exercise on the development of dietary obesity is different in males and females, and that sedentary male and female rats can both show persistent dietary obesity after withdrawal of the palatable foods.     

Neuroadaptive changes in mesocorticolimbic dopamine and acetylcholine neurons following cocaine or saline self-administration are dependent on pre-existing individual differences

Previously, we demonstrated that stress-induced self-grooming behaviour in rats predicted an enhanced motivation to self-administer cocaine as determined under a progressive ratio schedule of reinforcement. The enhanced motivation of high grooming (HG) rats was associated with a reduced reactivity of dopaminergic neurons in the medial prefrontal cortex and amygdala, but not nucleus accumbens. In the present study, we studied the effect of cocaine and saline self-administration on these pre-existing differences in neurochemical profile by determining the electrically evoked release of [3H]dopamine and [14C]acetylcholine from superfused slices of the nucleus accumbens shell and core, medial prefrontal cortex and amygdala of HG and low grooming (LG) rats. Although HG and LG rats did not differ in acquisition of cocaine and saline self-administration, both conditions induced substantially different neuroadaptations in these rats. Differences in depolarisation-induced dopamine and acetylcholine release were maintained in the medial prefrontal cortex, emerged in the nucleus accumbens and dissipated in the amygdala. These results indicate that altered reactivity of mesocorticolimbic dopaminergic and cholinergic neurons due to exposure to cocaine and environmental stimuli (saline) is dependent on pre-existing neurochemical differences and displays region-specificity. These pre-existing differences and the cocaine- and environmental-induced neuroadaptations seem to act in concert to produce an enhanced motivational state to self-administer cocaine.     

Cell-type specific increases in female hamster nucleus accumbens spine density following female sexual experience

Female sexual behavior is an established model of a naturally motivated behavior which is regulated by activity within the mesolimbic dopamine system. Repeated activation of the mesolimbic circuit by female sexual behavior elevates dopamine release and produces persistent postsynaptic alterations to dopamine D1 receptor signaling within the nucleus accumbens. Here we demonstrate that sexual experience in female Syrian hamsters significantly increases spine density and alters morphology selectively in D1 receptor-expressing medium spiny neurons within the nucleus accumbens core, with no corresponding change in dopamine receptor binding or protein expression. Our findings demonstrate that previous life experience with a naturally motivated behavior has the capacity to induce persistent structural alterations to the mesolimbic circuit that can increase reproductive success and are analogous to the persistent structural changes following repeated exposure to many drugs of abuse.     

Potentiation of amphetamine-induced locomotor activity following NMDA-induced retrohippocampal neuronal loss in the rat

The present experiment assessed the locomotor response to a low dose (1 mg/kg) of systemic gemd-amphetamine in rats with cytotoxic lesions of the retrohippocampus (entorhinal and extra-subicular cortices), compared with vehicle-operated shams and unoperated controls. Under spontaneous and saline conditions, both the sham and the lesioned animals were more active than unoperated controls, and they did not differ from each other. Systemic gemd-amphetamine produced increased locomotion in all groups, but this effect was potentiated in animals with retrohippocampal lesions; two control groups did not differ from each other in their response to the drug. The present results are consistent with the suggestion that cell loss within the retrohippocampal region could affect the functional response of nucleus accumbens to amphetamine. The results are discussed in terms of the interaction between the retrohippocampus and nucleus accumbens in the control of mesolimbic dopamine release and the possible implications for schizophrenia.     

High and low responders to novelty: effects of adrenergic agents on the regulation of accumbal dopamine under challenged and non-challenged conditions

The main goal of this study was to provide in vivo neurochemical evidence that mesolimbic alpha- and beta-adrenoceptors direct the release of mesolimbic dopamine. Both high responders to novelty and low responders to novelty were used to study the effects of intra-accumbal administered adrenergic agents on the dopamine release in the nucleus accumbens during two conditions, namely at rest (non-challenge) and when exposed to a "new cage" (challenge). Under non-challenged condition: phenylephrine (alpha-adrenergic agonist) induced a dose-dependent increase in dopamine release that was significantly larger in high responders; phentolamine (alpha-adrenoceptor antagonist) also induced a dose-dependent increase in dopamine that was significantly larger in low responders; isoproterenol (beta-adrenoceptor agonist) induced a dose-dependent increase in dopamine that did not differ between the two types of rat; propranolol (beta-adrenoceptor antagonist) did not change the dopamine release. Under challenged condition: phenylephrine and phentolamine both increased dopamine release without type-specific differences; only in low responders did isoproterenol increase the novelty-induced dopamine release; only in high responders did propranolol decrease the novelty-induced dopamine release.The in vivo neurochemical data are discussed in view of the outcome of earlier reported in vitro studies and pharmaco-behavioral studies. Overall the data reveal that mesolimbic noradrenaline has a dual role in the nucleus accumbens. It is argued that stimulation of alpha-adrenoceptors and beta-adrenoceptors, located postsynaptically on dopamine nerve-endings, inhibits and facilitates, respectively, dopamine release, whereas stimulation of presynaptic alpha-adrenoceptors inhibits the release of noradrenaline and, subsequently, disinhibits the release of dopamine. Moreover, it is argued that non-challenged high responders have a relatively low (alpha/beta) noradrenergic tonus that changes into a relatively high (alpha/beta) noradrenergic tonus during challenge, and that non-challenged low responders have a relatively high (alpha) adrenergic tonus that changes into a relatively low (alpha) noradrenergic tonus during challenge.In general, the present data clearly reveal that both alpha- and beta-adrenoceptors differentially regulate dopamine release in the nucleus accumbens. This regulation is individual-specific and depends on the test-condition (challenged versus non-challenged).     

Resistance of male Sprague-Dawley rats to sucrose-induced obesity: effects of 18-methoxycoronaridine

Evidence suggests that the development of obesity in males and females might be mediated by distinct mechanisms, warranting different treatment approaches. In previous studies from this laboratory, a high sucrose diet induced excessive weight gain in female Sprague-Dawley rats and administration of a selective antagonist of α3β4 nicotinic receptors, 18-methoxycoronaridine (18-MC), prevented this form of obesity. In the present study similar parameters were studied in male rats by using an identical experimental protocol. The effects of repeated administration of 18-MC on body weight gain, deposition of fat, consummatory behavior and biochemical markers of obesity in male rats were also assessed. In contrast to females, males consuming ad libitum quantities of sucrose solution (30%) in combination with normal chow did not become obese; they did not gain excessive weight nor show excessive fat deposition. Repeated administration of 18-MC (20 mg/kg, i.p.) attenuated weight gain in both sucrose-consuming and control animals without altering food or fluid intake. The present results indicate that males and females are differentially responsive to high carbohydrate-diet obesity. Such gender disparities could be secondary to sex-specific alterations in cholinergic mechanisms of feeding and body weight regulation.     

Comparison of somatodendritic and axon terminal dopamine release in the ventral tegmental area and the nucleus accumbens

Fast cyclic voltammetry at a carbon fibre microelectrode was used to measure dopamine release following electrical or chemical stimulation in rat brain slices incorporating either the ventral tegmental area or the core region of the nucleus accumbens. Electrical or chemical stimulation gave clear voltammetric signals which corresponded to dopamine; less dopamine was released in the ventral tegmental area than in the nucleus accumbens. In contrast to the nucleus accumbens, electrically stimulated dopamine release in the ventral tegmental area was not sensitive to tetrodotoxin, was not modified by the presence of dopamine uptake inhibitors, or agonist or blockers acting at dopamine D₂ autoreceptors.