Differential effects of amphetamine and food deprivation on self-stimulation of the lateral hypothalamus and medial frontal cortex.

Intracranial self-stimulation of the lateral hypothalamus in 5 male Sprague-Dawley rats was markedly increased by subcutaneous dextroamphetamine administration and by food deprivation. In contrast, similar self-stimulation response rates obtained in the same Ss from the medial frontal cortex were unaffected by food deprivation and only slightly increased by dextroamphetamine administration. Furthermore, a large difference between dextro- vs levoamphetamine on response rate was obtained for lateral hypothalamic but not for medial frontal cortex self-stimulation. Results are consistent with a noradrenergic self-stimulation system for the lateral hypothalamus. Medial frontal cortex self-stimulation, however, appears to be mediated by a neuroanatomical and neurochemical system different from that of the lateral hypothalamus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of morphine and pentazocine on thrombocyte functional activity

Apart from main classic neuron types there is a small group of neurons known in literature as intermediate Lugaro cells. Two Lugaro cells types are distinguished: fusiform and those with triangular cell body. Fusiform cells vary not only in vertical, horizontal or diagonal position of cell body, but also have certain morphological peculiarities. Axons of some fusiform cells project either to molecular layer or reach Purkinje cells layer or remain at the level of granular layer. Along with it, there are true intermediate cells, described by Lugaro. These cell processes project from layer to layer. Neurons with triangular cell body located at different granular layer levels relate to the second group of Lugaro cells. Due to great extension of their processes Lugaro cells possess projection area ranging from molecular layer to white substance. Lugaro cells are independent neurons, always present in cerebellar cortex.     

Attenuation of punishing effects of morphine and amphetamine by chronic prior treatment.

In a previous study L. Parker et al (see record 1973-20548-001) found that the gustatory aversion normally produced by morphine did not occur when rats were first made dependent on the drug. Their explanation of this phenomenon was that dependent, withdrawn animals are in an "unnatural need state" such that a taste stimulus paired with morphine will become preferred by pairing with a beneficial need-replenishing event. This explanation was examined in the present 2 experiments with a total of 180 male Wistar rats. In Exp I the Parker et al results were supported in a conceptually similar experiment. In Exp II it was shown that analogous results could be produced with amphetamine, a drug upon which physicial dependence has not been unequivocally demonstrated and for which the regulation of self-administration does not follow the morphine pattern. Since the evidence for a "need" artificially induced by amphetamine withdrawal was not strong, the hypothesis that these data reflect preference for a substance associated with need reduction may be questioned. Of the various explanations for the phenomenon, only one involving the concept of drug tolerance has no arguments against it. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute effects of morphine on rat intestinal motility

The cumulative urinary excretion over 24 h of pentazocine, under conditions of acidic urinary pH, has been measured in smokers and non-smokers using both male and female subjects (seventy subjects in total). A restricted urban population was studied. An overall three-fold inter-subject variation in elimination was observed. The cumulative urinary excretion of pentazocine was normally distributed in both smokers and non-smokers. Smokers metabolize 40% more pentazocine than non-smokers. It is concluded that induction is principally responsible for the observed subject variability.     

Effects of amphetamine, butorphanol, and morphine pretreatment on the maintenance and reinstatement of cocaine-reinforced responding

1. Flupirtine (Katadolon) is a member of a class of triaminopyridines and is used as a nonopioid analgesic agent with muscle relaxant properties. 2. In situ experiments have revealed that flupirtine protects against ischemic-induced insults to the retina and brain. 3. Data derived from in vitro and in vivo studies suggest that flupirtine functions as a weak N-methyl-D-aspartate (NMDA) antagonist with little evidence that it acts on AMPA-kainate type glutamate receptors. 4. No evidence could be found from binding studies to suggest that flupirtine has an affinity for any of the characterized binding sites associated with the NMDA receptor. 5. Studies on cultured cortical neurons show that the NMDA-induced influx of 45Ca2+ is more readily decreased by flupirtine when a reducing agent (dithiothreitol) is present. However, when N'-ethylmaleimide, which is thought to alkylate the NMDA receptor redox site, is present, no obvious effect on the NMDA-induced influx of 45Ca2+ is produced by flupirtine. 6. Flupirtine is also known to counteract the production of reactive oxygen species caused by ascorbate/iron as well as to prevent apoptosis in cells lacking NMDA receptors induced by oxidative stress. 7. To explain all the experimental data, it is suggested that flupirtine affects the redox state/pH/electrons in the cell. The specific way by which flupirtine antagonizes the NMDA receptor might be by an action on the known redox site of the receptor.     

Differential effects of buprenorphine and pentazocine on the regional cerebral metabolic rate for glucose in the conscious rat

The effects of buprenorphine (BNP, 10-200 micrograms/kg, i.v.) and pentazocine (PTZ, 2.5-10 mg/kg, i.v.) on the regional cerebral metabolic rate for glucose (rCMRglc) were analyzed in nine anatomically discrete areas of the conscious rat brain by the simultaneous use of [14C]2-deoxyglucose, the glucose analogue that can be phosphorylated in the brain, and [3H]3-O-methylglucose, a nonmetabolizable glucose analogue. Originally, this method was developed by Gjedde and Diemer in the rat and in humans. The rCMRglc was significantly decreased by BNP (100 or 200 micrograms/kg) in most of the brain regions investigated, except the cerebellum. In contrast, PTZ (10 mg/kg) significantly increased rCMRglc in the cerebral cortex and medulla. In the cerebral cortex and medulla, the direction of the effect on rCMRglc was opposite for BNP (22% decrease at the dose of 200 micrograms/kg) and PTZ (22% increase at the dose of 10 mg/kg). These findings strongly suggest that the discrepancies between the marked effects of BNP (a partial mu agonist and kappa antagonist) and PTZ (a mu antagonist and kappa agonist) on rCMRglc reflect the selectivity of agonist action at the different types of opioid receptors, mu and kappa receptors, in the rat brain.     

Posttraining intracranial self-stimulation ameliorates the detrimental effects of parafascicular thalamic lesions on active avoidance in young and aged rats.

To evaluate whether intracranial self-stimulation (SS) ameliorates conditioning deficits induced by parafascicular nucleus (PF) damage in young and aged rats, the authors gave rats a daily session of 2-way active avoidance until a fixed criterion was achieved. Four experimental groups were established in both young and aged rats: SS treatment after every conditioning session (SS groups), pretraining PF lesions (lesion groups), PF lesions and SS treatment (L + SS groups), and controls. SS treatment not only canceled the detrimental effects of PF lesions, but also improved conditioning in lesioned rats (L + SS groups). This effect was more powerful in aged rats. SS treatment compensated for memory deficits generated by hypofunctionality of arousal systems such as that involving the PF. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nicotine and brain-stimulation reward: interactions with morphine, amphetamine and pimozide

Using a rate-independent discrete trial method of determining thresholds for rewarding electrical intracranial stimulation in rats, we evaluated the pharmacological interaction of nicotine plus morphine, d-amphetamine, or the D2 receptor antagonist, pimozide. Both morphine and amphetamine shifted the dose-response curve for nicotine down and to the left, indicating increased efficacy and potency, respectively. Pimozide at doses that have no effect on performance and only minimal effect on brain-stimulation reward blocked the effect of nicotine. These data suggest that the same dopaminergic substrate that supports the positive reinforcing effects of other drugs of abuse also supports nicotine reward.     

Apomorphine and amphetamine produce differential effects on the speed and success of reaction time responding in the rat

Apomorphine, a nonselective, direct-acting dopamine agonist, and amphetamine, a nonselective indirect-acting dopamine agonist, were compared for their effects on the reaction time response in rats. Animals were shaped to release a lever in response to an auditory/visual stimulus to avoid mild foot shock. The characteristics of the reaction time response of primary interest were percent successful avoidance and response latency. Apomorphine (0, 1, and 5 mg/kg, IP) significantly decreased successful avoidance, but had no effect on response latencies. Thus, the decrease in successful avoidance was not a direct result of longer latencies. Amphetamine (0, 0.5, and 1 mg/kg, IP) produced a different pattern of effects on the reaction time response. Successful avoidance was not affected by amphetamine treatment. However, response latencies were dose-dependently decreased in response to amphetamine. These results demonstrate that dopamine receptor stimulation by different dopamine agonists produces a different pattern of effects on the characteristics of the reaction time response. In addition, these results demonstrate that successful avoidance can be modulated independently of response latencies.     

Tolerance to morphine in the rat: Associative and nonassociative effects.

Two experiments were conducted to examine the impact of dose level and interdose interval (IDI) on the development of tolerance to the analgesic effect of morphine. In Exp I, rats were administered a series of low- (5 mg/kg) or high- (30 mg/kg) dose injections of morphine either explicitly paired or unpaired with a distinctive context at a 48-hr IDI. The development of tolerance following this regimen was assessed by shifts in dose-response curves to the right when animals were tested on a tail-flick device in the distinctive context. Only animals that had received morphine paired with the distinctive context were tolerant to morphine; the magnitude of this associative tolerance was a positive function of the level of the conditioning dose. In Exp II, rats were exposed to a high dose of morphine (30 mg/kg) either paired or unpaired with a distinctive context at one of two IDIs (24 or 96 hr). Tolerance testing revealed that at the long IDI, only associative tolerance was evident, whereas at the short IDI, tolerance in the unpaired condition was more pronounced with a corresponding decline in the development of associative tolerance. The relevance of these findings for psychological theories of drug tolerance are discussed. Results are consistent with the predictions of an habituation model of drug tolerance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the effects of morphine and immobilization stress on discrimination performance of rats.

Compared the effects of morphine and immobilization stress (IMS) on performance of 24 male Sprague-Dawley rats in discrete-trial, 2-choice discrimination tasks. In Exps I and II, 2 shocks of different intensities were discriminative stimuli (DSs) for choices in a T-maze. In Exps III and IV, responses were right and left leverpresses in an operant chamber, where correct responses were signaled by either shocks of different intensities (shock discrimination task) or by the position of a brief light flash (light discrimination task). In Exp I, both 70-min IMS and 5 mg/kg morphine induced greater disruptions in trials in which the higher shock was the DS and there were no significant differences between treatments. However, in Exp II, only the effects of morphine were blocked by 10 mg/kg naltrexone. In Exp III, the effects of IMS and morphine were not selective with respect to shock level in the shock discrimination task, nor were they task (shock vs light) selective. The effect of morphine was significantly greater than the effect of IMS in both tasks. Exp IV indicated that effects induced by actual alterations in the intensities of the DS shocks did not mimic those induced by either morphine or IMS but that abrupt decreases in the duration of the DS lights induced effects similar to those of morphine. Results indicate that (a) different mechanisms mediate the effects of IMS and morphine and (b) many of their behavioral effects in shock discrimination tasks are due to dissociative processes rather than alterations in perceived shock intensity. (52 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of cholinergic agonists and antagonists on self-stimulation behavior in the rat.

Trained 23 male Wistar albino rats to press a bar for electrical stimulation of the brain on a 30-sec variable-interval schedule. Ss were tested weekly with 1 or more of the following drugs: physostigmine (50-400 MUg/kg), neostigmine (25-200 MUg/kg), atropine (2-16 mg/kg), methylatropine (2-16 mg/kg), scopolamine (400-1,600 MUg/kg), pilocarpine (500-4,000 MUg/kg), nicotine (100-800 MUg/kg), mecamylamine (1 mg/kg), and methamphetamine (500 MUg/kg). Results support the suggestion that the cholinergic system is composed of 2 reciprocally related components: (a) a muscarinic "no-go" portion, whose activation has an inhibitory effect on self-stimulation; and (b) a nicotinic "go" portion, whose excitatory effect on self-stimulation is (most probably) mediated by norepinephrine. (33 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of dopamine in maintaining intracranial self-stimulation in the ventral tegmentum, nucleus accumbens, and medial prefrontal cortex.

Male albino Wistar rats were prepared with 2 chronic bipolar electrodes implanted ipsilaterally in the ventral tegmentum and either the nucleus accumbens or the medial prefrontal cortex. Once stable intracranial self-stimulation was elicited from both midbrain and forebrain electrodes, 6-hydroxydopamine lesions were placed into the ascending dopaminergic pathways between the rewarding electrode placements at the level of the lateral hypothalamus. Data suggest that dopamine plays an important role in self-stimulation in the ventral tegmentum and contributes to this behavior in the prefrontal cortex. Findings also show that nondopaminergic systems contribute to the phenomenon of brain-stimulation reward. (French summary) (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned suppression of medial forebrain bundle and septal intracranial self-stimulation in the rat: Evidence for a fear-relief mechanism of the septum.

In 3 experiments, a conditioned emotional response (CER) paradigm was presented to 2 groups of male albino Sprague-Dawley rats (N?=?20) during intracranial self-stimulation (ICSS). One group barpressed for medial forebrain bundle (MFB) stimulation reward; the other group barpressed for septal stimulation reward. The MFB ICSS was found to be suppressed by the CER procedure, but this procedure failed to suppress septal ICSS. The difference between the 2 sites was found only when both MFB and septal ICSS current intensities were available at their optimal levels. When ICSS current intensities were lowered to either threshold or medium level, both groups exhibited the CER suppression effect. Ss were also tested for a possible analgesic effect produced by the ICSS. MFB stimulation was found to produce some degree of analgesia, but septal stimulation failed to produce any analgesic effect. Thus, the possibility that the attenuation of the CER suppression effect in the septal group was due to analgesia was excluded. The difference in MFB and septal ICSS behavior during the presentation of the aversive stimulus suggests a possible qualitative distinction between the reward functions of the 2 sites, and a possible fear-reduction property of the septal area. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reward versus performance in self-stimulation: Electrode-specific effects of !a-methyl-p-tyrosine on reward in the rat.

Tested the hypothesis that alpha-methylparatyrosine (AMPT), an inhibitor of catecholamine synthesis, reduces brain stimulation reward, using a measure of reward previously shown to be relatively unaffected by variables that alter performance but not reward; Ss were 14 male albino rats. The rewarding effectiveness of stimulation was determined by the location of the sharp rise in the function relating running speed in an alley to the number of pulses received as a reward. For some electrodes, AMPT depressed self-stimulation performance (speed of running) without producing any sizable effect on the measure of reward (location of rise). For other electrodes, the rewarding effectiveness of the stimulation was greatly reduced by AMPT and restored by levodopa. These opposing results could be repeatedly demonstrated on different electrodes in the same S. The electrode-specific differential sensitivity to AMPT suggests neurochemically disparate substrates for reward. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gabapentin enhances the antinociceptive effects of spinal morphine in the rat tail-flick test

The antinociceptive effects of the combination of spinal morphine and gabapentin were evaluated in the tail-flick test in rats. The intrathecal coadministration of a subantinociceptive dose of morphine at 0.2 microgram and gabapentin at 300 micrograms produced significant antinociception. Pretreatment with spinal gabapentin at 300 micrograms shifted the dose-response curve of spinal morphine to the left with a decrease in morphine ED50 value from 1.06 micrograms to 0.34 microgram. The antinociceptive effects produced by the combination of a subantinociceptive dose of morphine and gabapentin were reversed by spinal naloxone at 30 micrograms but were not reversed by spinal bicuculline at 0.3 microgram. Furthermore, the concurrent administration of spinal naloxone at 30 micrograms with the combination of morphine and gabapentin blocked antinociception, while the concurrent administration of spinal bicuculline at 0.3 microgram failed to prevent antinociception. These results indicate that the combination of spinal gabapentin and morphine produces an enhancement of antinociception that appears to involve the spinal mu opioid receptors. Furthermore, repeated administration of gabapentin for 3 days did not affect the enhancing effect of gabapentin on the antinociceptive effect of morphine, indicating that tolerance did not develop to gabapentin's ability to enhance morphine antinociception.