Age-related differences in MK-801- and amphetamine-induced locomotor and stereotypic activities of rats

Changes in locomotor and stereotypic activities induced by an i.p. injection of either (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cycloheptan-5,10-imine maleate (dizocilpine or MK-801; 0.3 mg/kg) or D-amphetamine sulfate (AMPH; 1.5 mg/kg) were studied in male Mill Hill hooded rats of different age. The following age groups of animals were considered: 28-30 postnatal day (PND)-old rats (peripubertal), 48-50 PND-old (pubertal), 3-month-old (adults), 12-month-old (middle-aged) and 24-month-old (aged). The motor response was measured by an automated animal activity measuring system. The obtained results showed that: (1) in contrast to AMPH, MK-801 induced more pronounced increases of both locomotor and stereotypic activities in peripubertal and pubertal than in adult and aged rats; (2) AMPH induced the same locomotor and stereotypic activity increase in pubertal, adult and middle-aged rats; (3) both AMPH and MK-801 led to a senescence-related decrease of motor activity. These data suggest that the balance of the glutamatergic and dopaminergic systems changes during aging. Such a change is important in understanding schizophrenia and the motor system decline observed in the later stages of life.     

An activity indicator of acute withdrawal depends on amphetamine dose in rats

A moderate dose of amphetamine (AMPH) produces hypoactivity around 20 h post-administration. This hypoactivity may be an indicator of an acute withdrawal state. The purpose was to see how AMPH doses affected the expression of this hypoactivity and, by inference, AMPH-induced acute withdrawal. Rats were housed in individual open fields, with free access to food and water. Light-dark cycles were scheduled such that drug-elicited patterns could be readily detected. Animals first received a series of eight control treatments, and then a series of 10 experimental treatments spaced at 33-h intervals. Different experimental treatment groups received saline, 1.0 mg/kg, 2.0 mg/kg, or 4.0 mg/kg AMPH. The effects of these treatments on 33-h patterns of locomotor activity were observed. Control treatments produced no systematic time-dependent changes in activity beyond the first hour post-treatment. All doses of AMPH produced typical short-term effects: They markedly increased locomotion and/or stereotypy during the first 3 to 6 h post-treatment. Acute and chronic administrations of the 2.0 and 4.0 mg/kg doses also produced similar changes in longer term activity patterns: They produced hypoactivity 20 h later, followed by a recovery of activity around hour 25 post-treatment. The timing of amphetamine-induced hypoactivity and acute withdrawal may be independent of dose over a wide range of doses. Time-dependent changes in AMPH-induced state may influence motivation and drug-related assessments. The methodology described here may provide an easy and rapid way to investigate the determinants of AMPH-induced hypoactivity and acute withdrawal.     

Latent inhibition, but not prepulse inhibition, is reduced during withdrawal from an escalating dosage schedule of amphetamine

The enhanced locomotor and stereotypic responses of the rat to repeated amphetamine (AMPH) administration are considered to be an animal model of positive schizophrenic symptoms. In contrast, behaviors observed during withdrawal from repeated AMPH are believed to model depression or anxiety. In the present study, the authors tested whether AMPH withdrawal might also elicit behaviors consistent with animal models of schizophrenia, specifically, disruptions in latent inhibition (LI) of 2-way active avoidance and prepulse inhibition (PPI) of startle. Rats treated with escalating doses of AMPH (6 days, 1-5 mg/kg ip) or saline were tested for LI and PPI during withdrawal. LI was eliminated by prior AMPH treatment in rats tested at 4, 13, and 28 days of withdrawal. In contrast, PPI did not differ between AMPH and control groups. These results support an interrelationship between repeated-AMPH and LI-disruption, but not PPI-disruption, models of schizophrenia.     

Cocaine-induced locomotor activity is enhanced by exogenous testosterone

Anabolic-androgenic steroids are synthetic derivatives of testosterone, which are increasingly abused by adolescent populations who also abuse psychoactive substances. All these compounds lead to complex behavioral syndromes and the effects of their interactions remain unclear. The main aim of the present study was to determine the influence of testosterone on the locomotor activity-promoting effect of cocaine on male mice in an open field. In the three experiments, animals received two injections: firstly, testosterone or peanut oil, and secondly, cocaine or saline solution. In Experiments 1 and 2, testosterone (or oil) and cocaine (or saline) were injected 45 and 10 min, respectively, prior to activity recording. In the first experiment, we studied the effects of testosterone (2 mg/kg) on locomotor activity induced by different doses of cocaine (2, 4, 8, 10 or 12 mg/kg). In Experiment 2, we explored the effects of supraphysiological doses of testosterone (2, 6, 10 or 14 mg/kg) on animals treated with 10 mg/kg cocaine. Finally, in the third experiment, 14 mg/kg testosterone or vehicle was administered 15, 30, 45 or 75 min before activity data collection to animals that received 10 mg/kg cocaine or saline. Testosterone itself had no effects on spontaneous locomotor activity and, as was expected, cocaine increased locomotor activity dose-dependently. Given together, testosterone enhanced the cocaine-induced hyperactivity although not dose-dependently, the highest effects being found 45 min after testosterone injection. The present study confirmed the existence of an interaction between testosterone and cocaine at the central nervous system.     

Cocaine sensitization in male quail: temporal, conditioning, and dose-dependent characteristics

Chronic cocaine administration typically results in increased locomotor activity, known as behavioral sensitization. Investigating the time course of locomotor activity across trials may provide a more detailed analysis of the temporal changes that might occur within sensitization. Prior research with rodents shows that the peak of locomotor activity shifts from acute to chronic drug administration. The purpose of the current experiment was to investigate acute versus chronic cocaine effects on locomotor activity in an avian species, Japanese quail, and to investigate whether this phenomenon is dose-dependent. Subjects received daily ip injections of saline or 5, 10, or 20 mg/kg cocaine for 20 days. Following each injection, birds were placed in standard locomotor activity chambers, and activity was recorded for 150 min. A cocaine challenge was given after a ten-day withdrawal period. Two retraining trials were given to re-establish cocaine responding prior to a saline challenge in the drug-paired environment. Results showed that repeated administration of the 10 mg/kg dose of cocaine enhanced activity across 120 min compared with acute administration. In contrast, repeated administration of the 20 mg/kg dose resulted in greater cocaine-induced activity for 60 min compared with acute administration. In addition, behavioral sensitization was shown to be dose-dependent and appeared to be due, at least in part, to conditioning.     

Effects of single and group housing conditions and alterations in social and physical contexts on amphetamine-induced behavioral sensitization in rats

Repeated administration of amphetamine (AMPH) can produce behavioral sensitization. However, whether contextual elements and housing conditions influence AMPH-induced behavioral sensitization remains uncertain. This study was designed to examine the effects of housing conditions (single- vs. group-housed) and different contextual changes, including social (with two other co-drug partners) and physical (novel box) context changes, on AMPH-induced behavioral sensitization. During the training phase, all rats were exposed for 7 days to AMPH (1 mg/kg, intraperitoneally) in a Locometer chamber, with the exception of animals tested for the effects of physical context changes trained in a novel box. Following a 7-day withdrawal phase, all rats received an AMPH (0.5 mg/kg) challenge, and locomotor activity in a Locometer box was recorded before and after AMPH injection during the testing phase. Under group housing conditions, animals exposed to a different physical environment between the training and testing phases or accompanying co-drug partners during the training phase exhibited decreased AMPH-induced locomotor sensitization. In contrast, single housing conditions did not have an inhibitory effect on AMPH-induced behavioral sensitization after manipulations of the physical and social contexts. These results suggest that under group housing conditions, both physical and social context changes can attenuate AMPH-induced behavioral sensitization. The possible neural mechanisms underlying the involvement of different housing conditions in AMPH-induced behavioral sensitization are discussed.     

A comparison of the physiological, behavioral, neurochemical and microglial effects of methamphetamine and 3,4-methylenedioxymethamphetamine in the mouse

3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) are amphetamine analogues with similar persistent neurochemical effects in the mouse which some have described as neurotoxicity. We attempted to identify dose regimens of MDMA and METH with similar effects on behavioral and physiological variables in the mouse, then quantified the effects of these dose regimens on neurochemistry and microglial markers. Four discrete injections of saline, MDMA (10, 20, or 30 mg/kg), or METH (5 or 10 mg/kg) were administered to mice at 2 h intervals. Body weight was quantified immediately before each injection, and 2 h after the last injection, while core temperature and locomotor activity were continuously monitored via radiotelemetry. Mice were killed 72 h after the final injection and brains were rapidly dissected on ice. Dopamine content in various brain regions was quantified via high pressure liquid chromatography (HPLC), and microglial activation was assessed by saturation binding of the peripheral benzodiazepine receptor (PBR) ligand 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ([(3)H]PK11195). Specific dose regimens of MDMA and METH induced similar reductions in body weight, depletions of dopamine and its metabolites, and similar hyperthermic and locomotor stimulant effects, but only METH activated microglia in striatum. These results suggest that repeated high doses of MDMA and METH that produce hyperthermia, locomotor stereotypy, weight loss and neurochemical depletion are not consistently accompanied by microglial activation. The finding that METH, but not MDMA, induces microglial effects in the striatum consistent with neurotoxicity might imply different mechanisms of toxic action for these two psychostimulants.     

吗啡剂量及给药方式对大鼠运动敏感化的影响

目的:比较不同剂量吗啡皮下注射及给药方式(每日三次给药与每日一次给药)对Sprague-Dawlev大鼠运动敏感化的影响.方法:实验大鼠共分为五组,即生理盐水组、吗啡每日一次皮下注射组(1mg/kg组、3mg/kg组及10mg/kg组)以及吗啡每日三次皮下注射组(10mg/kg,次),每组8只大鼠.连续用药7天,隔日检测大鼠自发活动,然后停止药物处理,停药7天后每组大鼠予以吗啡3mg/kg皮下注射并检测大鼠自发活动.结果:吗啡每日一次皮下注射组中,各剂量组大鼠的运动敏感化均能顺利表达.吗啡每日三次皮下注射组大鼠的运动敏感化表达受到了抑制.结论:低剂量吗啡同样诱发运动敏感化,提示低剂量吗啡也会出现觅药动机敏感化,因此不要冒险尝试毒品即便是低剂量毒品;当每日一次间断用药时,运动敏感化更容易表达,提示负性强化可能是运动敏感化的调节机制之一.     

Time-course and dose-response relationships of imperatorin in the mouse maximal electroshock seizure threshold model

This study was designed to evaluate the anticonvulsant effects of imperatorin (a furanocoumarin isolated from fruits of Angelica archangelica) in the mouse maximal electroshock seizure threshold model. The threshold for electroconvulsions in mice was determined at several times: 15, 30, 60 and 120 min after i.p. administration of imperatorin at increasing doses of 10, 20, 30, 40, 50 and 100 mg/kg. The evaluation of time-course relationship for imperatorin in the maximal electroshock seizure threshold test revealed that the agent produced its maximum antielectroshock action at 30 min after its i.p. administration. In this case, imperatorin at doses of 50 and 100 mg/kg significantly raised the threshold for electroconvulsions in mice by 38 and 68% (P<0.05 and P<0.001), respectively. The antiseizure effects produced by imperatorin at 15, 60 and 120 min after its systemic (i.p.) administration were less expressed than those observed for imperatorin injected 30 min before the maximal electroshock seizure threshold test. Based on this study, one can conclude that imperatorin produces the anticonvulsant effect in the maximal electroshock seizure threshold test in a dose-dependent manner.     

褪黑素对胃肠运动的影响

目的: 研究不同浓度褪黑素(melatonin)对小鼠胃肠运动的影响。方法: 雄性C57BL小鼠腹腔内注射1 mg/kg、5 mg/kg、50 mg/kg和75 mg/kg浓度的褪黑素,分别在15 min和45 min后,检测结肠排出玻璃珠的变化;同时,在注射褪黑素75 mg/kg前腹腔内注射褪黑素拮抗剂luzindole(5 mg/kg),研究其对褪黑素作用的影响。另外,通过全胃肠道运输实验(伊文斯蓝排出实验)检测腹腔内注射不同浓度褪黑素(1 mg/kg、5 mg/kg、25 mg/kg和75 mg/kg)时胃肠运动的变化。结果: 腹腔内注射褪黑素后15 min,在低剂量组(1 mg/kg)结肠排出玻璃珠的时间缩短,与对照组比较差异显著(P<0.01);在高剂量组(75 mg/kg)结肠排出玻璃珠的时间明显延长(P<0.01),该抑制作用可被褪黑素拮抗剂luzindole有效拮抗(P<0.01)。腹腔内注射褪黑素后45 min,在5 mg/kg剂量时,结肠排出玻璃珠的时间明显缩短(P<0.01);而在1 mg/kg和50 mg/kg时,与对照组比较并无显著差异;在高剂量组(75 mg/kg)结果同上,即结肠排出玻璃珠的时间延长(P<0.05)。在胃肠道运输实验中,腹腔内注射褪黑素1 mg/kg和5 mg/kg后,运输时间缩短,排出伊文斯蓝粪粒所需时间减少,与对照组比较差异显著(均P<0.01);大剂量褪黑素(75 mg/kg)也明显延长胃肠道运输时间(P<0.01)。结论: 低剂量褪黑素促进胃肠运动,高剂量褪黑素降低胃肠运动,后者作用可被褪黑素受体拮抗剂luzindole阻断。     

Effect of calcium channel blockers on cerebral ischemia-induced hyperactivity in Mongolian gerbils.

When both common carotid arteries of Mongolian gerbils were occluded for 5 min to produce ischemic insult, locomotor activity was increased the following day. The effect of calcium channel blockers on this ischemia-induced hyperactivity was investigated. Nimodipine, at doses of 5, 10, and 20 mg/kg, dose dependently and significantly decreased ischemia-induced hyperactivity. Nicardipine significantly decreased ischemia-induced hyperactivity and doses of 10 and 20 mg/kg. Nifedipine and flunaridine also significantly decreased ischemia-induced hyperactivity at doses of 20 mg/kg. Verapamil had no effect on ischemia-induced hyperactivity at a dose of 20 mg/kg. These findings suggest that ischemia-induced hyperactivity is related to calcium channels. These relationship between calcium channels and dopaminergic function is discussed.     

Long-term changes in the diabetic state induced by different doses of streptozotocin in rats

The long-term effects of different doses (0, 25, 35, 45, 55, 65 and 100 mg/kg) of streptozotocin (STZ) in male Wistar rats had been followed over a 16 week period. The weight-gain curve and the epididymal fat pad weight were significantly different (P less than 0.05) from control after 1 week with the 65 and 100 mg/kg doses and after 4 weeks with the 45 and 55 mg/kg doses; there were no significant changes with the 25 and 35 mg/kg doses even after 16 weeks. An i.v. glucose tolerance test (0.5 g/kg) was performed at 1, 4 or 16 weeks after the injection of STZ. The basal levels of glucose were significantly elevated (P less than 0.05) after 1 week with the greater than or equal to 55 mg/kg doses, and after 16 weeks with the greater than or equal to 45 mg/kg doses; there was also an overall increase in the basal glucose levels between 1 and 16 weeks in rats treated with the greater than or equal to 45 mg/kg doses. The basal insulin levels were significantly decreased (P less than 0.05) after 1 week with the greater than or equal to 65 mg/kg doses, after 4 weeks with the greater than or equal to 55 mg/kg doses and after 16 weeks with the greater than or equal to 35 mg/kg doses. The insulin peak 2 min after the glucose load was significantly less (P less than 0.05) after 1 week with the greater than or equal to 35 mg/kg doses and after 16 weeks with the greater than or equal to 25 mg/kg doses. The use of an insulinogenic index to assess the insulin secretory capacity showed a significant decrease (P less than 0.05) for the greater than or equal to 35 mg/kg doses at each tested time; with the 45 mg/kg dose, there was a further significant decrease (P less than 0.01) between the first and sixteenth week. The present long-term studies showed that there is a progressive deterioration in the glucose tolerance and insulin secretion after the injection of different doses of STZ. Furthermore, changes in glucose-insulin interrelationships over time suggest that the insulin insensitivity previously described in STZ diabetic rats might be only an early transient phenomenon.     

The influence of dfp, atropine and toxogonine on tryptophan pyrolase activity in mouse liver.

It was found that fluorostigmine (DFP) in doses 0-4 mg/kg i.p. reduced significantly tryptophan pyrolase activity in mouse liver homogenates.se liver homogenates 120 and 180 min after the administration of the drug. On the other hand, fluorostigmine administered in doses 0-8 mg/kg i.p. increases the activity of the enzyme studied at 30 and 60 min after the injection. DFP (0.4 mg/kg i.p.) given in combination with atropine (10 mg/kg i.p.) causes a significant increase in enzyme activity determined 30, 60, 120 and 180 min after the administration of the drug. Toxogonine (in doses 5 mg/kg s.c.) given together with DFP (0.4 mg/kg i.p.) intensifies the activity of tryplophan pyrolase at 180 min after their administration. Simultaneous treatment with toxogonine (5 mg/kg s.c.), atropine (10 mg/kg i.p.) and DFP (0.4 MG/KG I.P.) reduced significantly the activity of the enzyme studied at all time of determination. Moreover, the experiment in vitro showed that DFP in concentrations of 4x10(-9) M; 8X10(-9) M; 1.6X10(-8) M and 3.2x10(-8) M increased tryptophan pyrolase activity in mouse liver homogenates.     

Long-term changes in the diabetic state induced by different doses of streptozotocin in rats.

The long-term effects of different doses (0, 25, 35, 45, 55, 65 and 100 mg/kg) of streptozotocin (STZ) in male Wistar rats had been followed over a 16 week period. The weight-gain curve and the epididymal fat pad weight were significantly different (P less than 0.05) from control after 1 week with the 65 and 100 mg/kg doses and after 4 weeks with the 45 and 55 mg/kg doses; there were no significant changes with the 25 and 35 mg/kg doses even after 16 weeks. An i.v. glucose tolerance test (0.5 g/kg) was performed at 1, 4 or 16 weeks after the injection of STZ. The basal levels of glucose were significantly elevated (P less than 0.05) after 1 week with the greater than or equal to 55 mg/kg doses, and after 16 weeks with the greater than or equal to 45 mg/kg doses; there was also an overall increase in the basal glucose levels between 1 and 16 weeks in rats treated with the greater than or equal to 45 mg/kg doses. The basal insulin levels were significantly decreased (P less than 0.05) after 1 week with the greater than or equal to 65 mg/kg doses, after 4 weeks with the greater than or equal to 55 mg/kg doses and after 16 weeks with the greater than or equal to 35 mg/kg doses. The insulin peak 2 min after the glucose load was significantly less (P less than 0.05) after 1 week with the greater than or equal to 35 mg/kg doses and after 16 weeks with the greater than or equal to 25 mg/kg doses. The use of an insulinogenic index to assess the insulin secretory capacity showed a significant decrease (P less than 0.05) for the greater than or equal to 35 mg/kg doses at each tested time; with the 45 mg/kg dose, there was a further significant decrease (P less than 0.01) between the first and sixteenth week. The present long-term studies showed that there is a progressive deterioration in the glucose tolerance and insulin secretion after the injection of different doses of STZ. Furthermore, changes in glucose-insulin interrelationships over time suggest that the insulin insensitivity previously described in STZ diabetic rats might be only an early transient phenomenon.     

Facilitatory effects of WAY-100635, a 5-HT1A receptor antagonist, on lordosis in female rats

Effects of the serotonin (5-HT) receptor 1A antagonist, WAY-100635, on lordosis in female rats were examined. Ovariectomized rats were implanted with a silicon tube containing estradiol and behavioral tests were performed. Next, 5, 10 or 20 mg/kg bw WAY-100635 or saline was injected subcutaneously in female rats with a lordosis quotient (LQ) from 10 to 30 and the behavioral test was performed again. As a result, the mean LQs in 10 or 20 mg WAY-100635-treated groups were higher than in the saline-treated group (P < 0.01 and P < 0.05, 10 or 20 mg groups versus saline, respectively). In the experiment on the time-course of change in LQ after injection with 10 mg WAY-100635, the mean LQ was increased (P < 0.01, versus saline) 15 min after the injection and high levels persisted for 1 h. This finding shows that WAY-100635 has the potency to enhance lordosis behavior acutely in female rats with a low estrous state. In order to investigate relationships between the 5-HT(1A) receptor and the GABA(B) receptor in regulating lordosis, 10 mg baclofen, a GABA(B) receptor agonist, was injected and this was followed 1 h later by the injection of 10 mg/kg WAY-100635. Mean LQ decreased after the injection of baclofen (P < 0.0001, versus placebo-treated control), but the decrease in LQs was not reversed by injection with WAY-100635.     

Adaptations in medial prefrontal cortex function associated with amphetamine-induced behavioral sensitization

Neuroadaptations in the prefrontal cortex (PFC) are hypothesized to play an important role in the behavioral changes associated with repeated psychostimulant exposure, but there are few published studies that measure neuronal activity during the development and expression of sensitization. To address this, we recorded single neuron activity in the medial PFC (mPFC) of male rats that were exposed for 5 days to saline or amphetamine (AMPH; 1.0 mg/kg i.p.) and then given saline or AMPH challenges following a three-day withdrawal. We found that rats exposed to AMPH developed locomotor sensitization to the drug that emerged on the fifth treatment session and became statistically significant at AMPH challenge. This was associated with no change in baseline (i.e., pre-injection) activity of mPFC neurons across the treatment or challenge sessions. Following the first AMPH injection, mPFC neurons responded primarily with reductions in firing, with the overall pattern and magnitude of responses remaining largely similar following repeated treatment. The exception was in the minority of cells that respond to AMPH with increases in firing rate. In this population, the magnitude of excitations peaked during the fifth AMPH exposure and was still relatively elevated at the AMPH challenge. Furthermore, these units increased firing during a saline challenge that was given to assess associative conditioning. These results suggest that AMPH-induced adaptations in mPFC function are not as apparent as AMPH-induced adaptations in behavior. When mPFC adaptations do occur, they appear limited to the population of neurons that increase their firing in response to AMPH.     

Effect of gabaergic, glutamatergic, antipsychotic and antidepressant drugs on pilocarpine-induced seizures and status epilepticus

This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Fluoxetine (10 and 20 mg/kg), NMDA (N-methyl-D-aspartate, 10 and 20 mg/kg), amitriptyline (25 and 50 mg/kg), ketamine (0.5 and 1.0 mg/kg), gabapentin (100 and 150 mg/kg) and pimozide (10 and 20 mg/kg) were administered intraperitoneally, 30 min prior to pilocarpine (400mg/kg, s.c.). The animals were observed (24h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. Fluoxetine, amitriptyline, NMDA, and pimozide had proconvulsant effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures and/or mortality. Gabapentin and ketamine protected against seizures and reduced the latency to first seizure. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with epilepsy because of the possibility of potentiating convulsive process toxicity.     

Effects of cadmium on cocaine-induced changes in activity.

Adult male rats were exposed to a diet that contained 100 parts per million added cadmium or a control diet for 72 days before being tested in a Digiscan activity monitor. During the 1-hr test period, each animal's baseline activity levels were recorded for 20 min. Animals then received intraperitoneal injections of 0, 10, 20, or 40 mg/kg cocaine HCl, and their activity levels were recorded for the remaining 40 min of the test session. The results showed that the 10, 20, and 40 mg/kg doses of cocaine produced behavioral activation in the control-diet animals. For cadmium-treated animals, cocaine-induced behavioral changes at the 10 mg/kg dose were not observed, but increased activity was evident at the two higher doses.     

Stimulation of the LH release by naloxone in anaesthetized cats after ovariectomy

The effect of intravenous injections or infusions of the opioid receptor antagonist naloxone on the secretion of luteinizing hormone (LH) was studied in 18 spayed cats anaesthetized with Althesin. Effective injections significantly increased the LH concentration of plasma samples (taken every 10-15 min and measured by radio-immunoassay) to a peak 20-30 min after injection. The concentration thereafter declined exponentially (ke = 0.42), and, in 4/8 trials rose again significantly and declined again without further injection. The threshold dose was between 0.4 and 0.5 mg/kg. There did not appear to be a dose dependence of the effect above threshold. Infusion of naloxone at levels up to 5 mg/kg/h was effective in producing a pulsatile release of LH and repeated injections of threshold doses (0.5 mg/kg) could produce a maintained plateau and pulsatile release at frequencies comparable to pulse frequencies in vivo.     

Deletion of the GluR5 subunit of kainate receptors affects cocaine sensitivity and preference

We have demonstrated previously that mice expressing a constitutive deletion of the kainate receptor subunit GluR5 (GluR5 KO) do not differ from wildtype (WT) littermates of a congenic C57BL/6 background with regard to both the development of morphine physical dependence as measured by naloxone-precipitated withdrawal signs and to morphine reward as revealed by the expression of conditioned place preference (CPP). However, unlike WT, GluR5 KO mice fail to develop antinociceptive tolerance following repeated systemic morphine administration. In this report, we examined the impact of GluR5 deletion on cocaine-mediated CPP and locomotor sensitization. Expression of CPP was evident in WT mice following repeated daily administration of 20 mg/kg (but not 10 mg/kg) i.p. cocaine. Interestingly, GluR5 KO mice exhibited enhanced cocaine preference as compared with WT mice at both 10 and 20 mg/kg doses. In addition, while GluR5 KO mice did not differ from WT with respect to baseline locomotor activity, mutant mice demonstrated increased locomotor hyperactivity versus WT mice after repeated injection of 15 mg/kg i.p. cocaine. Collectively, these data indicate that GluR5 appears to negatively modulate some psychostimulant and rewarding properties of cocaine, as demonstrated by heightened sensitization and salience in mutant mice.