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N M White

Publications and source records attributed to N M White.

At least 37 records · Page 2Linked to original sources
PubMed1996

Increase in vasoactive prostaglandin E production after perfusion in human placental cotyledons.

Studies from our laboratory indicate that prostaglandins may be mediators of at least some of the teratogenic actions of ethanol in both mouse and human tissue model systems. The present studies were designed to evaluate the relationship between ethanol and prostaglandin E (PGE) production in isolated human placental cotyledons. Placentas were obtained immediately after cesarean section delivery. A fetal artery supplying a single cotyledon was identified and cannulated, and the isolated cotyledon was placed in a perfusion chamber where maternal circulation was established and dual circulation continued throughout the perfusion procedure. Antipyrine clearance, oxygen consumption, and placental production of human chorionic gonadotropin were measured to verify tissue viability. PGE levels of the perfusate were measured by radioimmunoassay. Study 1 evaluates the effect of perfusion with 25 and 100 mM ethanol on placental PGE production. It was found that PGE production increased after perfusion with 25 mM ethanol, but not during the perfusion period per se. The paradigm for study 2 was identical to that of study 1, with the addition of a buffer washout period after 100-mM ethanol perfusion. Again, results indicate that perfusate PGE levels were increased in the buffer washout periods after the 25-mM and the 100-mM ethanol perfusions. The effect was not concentration dependent. An increase in circulating PGE associated with ethanol administration may be teratogenic actions and represent a potential mechanism underlying at least some aspects of fetal alcohol syndrome.

Adult↗
PubMed1996

Addictive drugs as reinforcers: multiple partial actions on memory systems.

This review applies some new experimental findings and theoretical ideas about how reinforcers act on the neural mechanisms of learning and memory to the problem of how addictive drugs affect behaviour. A basic assumption of this analysis is that all changes in behaviour, including those involved in drug addiction and the initiation of drug self-administration, require the storage of new information in the nervous system. Animal studies suggest that such information is processed in several (this review deals with three) more or less independent learning and memory systems in the mammalian brain. Reinforcers can interact with these systems in three ways: they activate neural substrates of observable approach or escape responses, they produce unobservable internal states that can be perceived as rewarding or aversive, and they modulate or enhance the information stored in each of the memory systems. It is suggested that each addictive drug maintains its own self-administration by mimicking some subset of these actions. Evidence supporting the notion of multiple memory systems and data on the actions of several drugs (amphetamine, cocaine, nicotine, alcohol and morphine) on these systems are briefly reviewed. The utility of the concept of "reward" for understanding the effects of drugs on behaviour is discussed. Evidence demonstrating actions of drugs on multiple neural substrates of reinforcement suggests that no single factor is likely to explain either addictive behaviour in general or self-administration in particular. Some of the findings on the development and maintenance of self-administration by animals of the five exemplar drugs are discussed in the context of these ideas.

Amphetamines↗
PubMed1995

Information acquired by the hippocampus interferes with acquisition of the amygdala-based conditioned-cue preference in the rat.

White and McDonald (1993, Behav Brain Res 55:269-281) previously reported that animals with amygdala lesions failed to acquire a conditioned-cue preference (CCP) based on spatial cues, but that animals with fornix lesions exhibited larger CCPs of this type than normal animals. The present experiments focused on the hippocampal interference with amygdala-based CCP learning inferred from this finding. In experiment 1 we tested the hypothesis that this interference was due to the acquisition of information about the maze and its environment during a 10 min period of free exploration of the maze before the start of CCP training, hitherto given to all animals in these experiments. Normal animals that were not preexposed to the maze and animals that were preexposed to a similar maze in a different room both exhibited larger CCPs than animals that were preexposed to the same maze in the same room as CCP training and testing. This suggests that normal animals acquire context-specific information during the preexposure period and that this may be the cause of the hippocampus-based interference with the amygdala-mediated CCP. In experiment 2 we attempted to determine if the information thought to be acquired by the hippocampal memory system interferes with acquisition or expression of the CCP. As previously demonstrated, animals that received fornix lesions before preexposure (i.e., before the start of the experiment) exhibited larger than normal CCPs. Animals that received fornix lesions after preexposure but before CCP training and animals that received fornix lesions after CCP training but before testing both exhibited normal CCPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1995

Hippocampal and nonhippocampal contributions to place learning in rats.

Brain structures thought to be critical for learning and memory were lesioned, and the effects on rats' ability to locate food on a radial maze in situations that provided different types of information was used to suggest general principles of information processing by hypothesized neural systems that include each of the lesioned structures. When animals were confined to food-containing and empty arms on different training trials, the learned discrimination between the arms was amygdala based. More training trials were required for ambiguous (adjacent arms) than for unambiguous (widely separated arms) discriminations. When rats moved around and entered both food and no-food arms on the same trial, the unambiguous discrimination was learned by both dorsal striatum- and hippocampus-based systems; however, the ambiguous discrimination was learned only by the hippocampus system.

Amygdala↗
PubMed1994

Parallel information processing in the water maze: evidence for independent memory systems involving dorsal striatum and hippocampus.

This experiment investigated the ability of rats with dorsal striatal or fornix damage to learn the location of a visible platform in a water maze. We also assessed the animals' ability to find the platform when it was hidden (submerged). Rats with neurotoxic damage to the dorsal striatum acquired both the visible and hidden platform versions of the task, but when required to choose between the spatial location they had learned and the visible platform in a new location they swam first to the old spatial location. Rats with radio-frequency damage to the fornix acquired the visible platform version of the water maze task but failed to learn about the platform's location in space. When the visible platform was moved to a new location they swam directly to it. Normal rats acquired both the visible and hidden platform versions of the task. These findings suggest that in the absence of a functional neural system that includes dorsal striatum, spatial information predominantly controlled behavior even in the presence of a cue that the animals had previously been reinforced for approaching. In the absence of a functional hippocampal system behavior was not affected by spatial information and responding to local reinforced cues was enhanced. The results support the idea that different neural substrates in the mammalian nervous system acquire different types of information simultaneously and in parallel.

Animals↗
PubMed1993

Acquisition of a spatial conditioned place preference is impaired by amygdala lesions and improved by fornix lesions.

This experiment examined the role of the lateral nucleus of the amygdala, the hippocampus and the dorsal striatum in the acquisition of a conditioned place preference (CPP). The CPP was established on a radial maze which was rotated before each daily trial so that only distal cues could be used to distinguish among locations on it. Each rat was assigned a paired location in which the arm contained food, and an unpaired location in which the arm was empty. A training trial consisted of 30-min confinements in the paired and unpaired locations on successive days. Groups of animals received between 1 and 4 training trials, after which they were tested for their preference between their two assigned locations with no food in either one. Normal animals acquired a CPP after 4 training trials, an instance of stimulus--reward learning. Electrolytic and neurotoxic lesions of the lateral nucleus of the amygdala prevented acquisition of the CPP in 4 training trials, suggesting that some function of this structure (or of a neural system that includes it) is required for acquisition and/or expression of stimulus--reward associations. Striatal lesions had no effect on the CPP. Fornix lesions facilitated acquisition of the CPP after 1-3 training trials, but no CPP was observed in animals with combined fornix and amygdala lesions, suggesting that exposure to the maze environment led to the processing of information in a hippocampal system that interfered with acquisition or expression of the amygdala-based CPP. Fornix lesions also increased the number of entries into maze arms on the test day, and concurrent amygdala lesions attenuated this increase. This finding suggests that the increase in arm entries may have been generated by the amygdala and suppressed by the hippocampus. Arm entries were interpreted as an instance of a particular type of exploratory behavior. Therefore, the present results suggest that a neural system including the lateral nucleus of the amygdala mediates both stimulus--reward learning and at least one form of exploration, possibly through its connections with the motor output system in ventral striatum. A hippocampal system appears to suppress or interfere with both of these behaviors in normal animals.

Amygdala↗
PubMed1993

The ventral pallidum area is involved in the acquisition but not expression of the amphetamine conditioned place preference.

The present study examined the roles of the ventral pallidum area, one output system of the nucleus accumbens, in the acquisition and expression of the amphetamine conditioned place preference (CPP). Pre-conditioning NMDA lesions of the ventral pallidum area completely abolished the acquisition of the CPP. By contrast, post-conditioning NMDA lesions of the same area had no effect on the expression of the CPP. These results suggest that the ventral pallidum area mediates some process that involves the primary, but not conditioned rewarding effects of amphetamine.

Analysis of Variance↗
PubMed1993

Memory enhancement by post-training peripheral administration of low doses of dopamine agonists: possible autoreceptor effect.

These experiments examined the effect of post-training injections of low doses of dopamine (DA) agonists on the acquisition of two 8-arm radial maze tasks. On a winstay simultaneous discrimination task, a light cue signaled the location of food in four randomly selected arms on each trial, and animals were required to visit each of the lit arms twice within a trial. Animals received one food trial per day and were injected immediately after training on Day 5. The direct DA receptor agonist, apomorphine (0.05 mg/kg), and the direct D2-DA receptor agonists, LY 177555 (quinpirole: 0.05, 0.1 mg/kg) and B-HT 920 (0.05 mg/kg), all improved acquisition of winstay radial maze behavior relative to saline-injected controls. On a win-shift task, rats were allowed to obtain food from four randomly selected maze arms, followed by a delay period in which they were removed from the maze. Animals were returned to the maze for a retention test in which only those arms that had not been visited prior to the delay contained food. After training on shorter delays, a delay of 18 h was imposed between the first four and second four choices, and DA agonists were injected immediately after the first four choices. Apomorphine, LY 171555, and B-HT 920 (all at 0.05 mg/kg), all improved win-shift retention relative to saline-injected controls. On both tasks, delaying the injections for 2 h post-training eliminated the memory-improving effects of all drugs. The results indicate that post-training administration of DA agonists at doses that may preferentially stimulate autoreceptors improves memory.

Animals↗
PubMed1993

A triple dissociation of memory systems: hippocampus, amygdala, and dorsal striatum.

This study investigated the respective roles of the hippocampus, the amygdala, and the dorsal striatum in learning and memory. A standard set of experimental conditions for studying the effects of lesions to the three brain areas using an 8-arm radial maze was used: a win-shift version, a conditioned cue preference (CCP) version, and a win-stay version. Damage to the hippocampal system impaired acquisition of the win-shift task but not the CCP or win-stay tasks. Damage to the lateral amygdala impaired acquisition of the CCP task but not the win-shift or win-stay tasks. Damage to the dorsal striatum impaired acquisition of the win-stay task but not the win-shift or CCP tasks. These results are consistent with the hypothesis that the mammalian brain may be capable of acquiring different kinds of information with different, more-or-less independent neural systems. A neural system that includes the hippocampus may acquire information about the relationships among stimuli and events. A neural system that includes the amygdala may mediate the rapid acquisition of behaviors based on biologically significant events with affective properties. A neural system that includes the dorsal striatum may mediate the formation of reinforced stimulus-response associations.

Amygdala↗
PubMed1992

Pipradrol conditioned place preference is blocked by SCH23390.

We investigated the effect of the selective D1 dopamine antagonist, SCH23390, on the establishment of a pipradrol-conditioned place preference (CPP). Among various doses of pipradrol (6.25-75.0 mg/kg, SC), a CPP was established at 25.0 mg/kg. SCH23390 (0.16 mg/kg, IP) blocked the establishment of a CPP by this dose of pipradrol. The results suggest that pipradrol produces a rewarding effect and that this effect may involve activation of D1 dopamine receptors.

Animals↗
PubMed1991

The amphetamine conditioned place preference: differential involvement of dopamine receptor subtypes and two dopaminergic terminal areas.

We investigated involvement of dopamine receptor subtypes and two dopaminergic terminal areas in the acquisition and the expression of the amphetamine conditioned place preference (CPP). When injected systemically before conditioning, both D1 and D2 dopamine antagonists blocked acquisition in a dose-dependent manner. When injected systemically before testing, the effects of the same D1 and D2 antagonists differed. The selective D1 antagonist SCH23390 dose-dependently blocked expression of the previously established conditioned behavior within the dose range that also blocked acquisition. In contrast, D2 antagonists failed to block expression of the amphetamine CPP at doses which blocked acquisition. Expression was, however, blocked by higher doses of D2 antagonists, which may have lost their selectivity for the D2 dopamine receptor. The expression of the CPP was also blocked by microinjections of SCH23390 or sulpiride into nucleus accumbens, but not into striatum. In a control experiment, sodium pentobarbital, which significantly reduced spontaneous locomotor activity in a manner similar to the higher doses of the dopamine antagonists, had no effect on the expression of the amphetamine CPP when given before testing. Finally, electrolytic lesions of the dorsal striatum potentiated the amphetamine CPP. These findings indicate that the dopamine released by amphetamine interacts with both D1 and D2 dopamine receptors to establish a CPP, but that the expression of the CPP may involve activation of the D1 dopamine receptor in the nucleus accumbens.

Animals↗
PubMed1991

Place conditioning with dopamine D1 and D2 agonists injected peripherally or into nucleus accumbens.

The conditioned place preference technique was used to assess the affective properties of the direct dopamine D1 agonist, SKF38393, and the direct D2 agonist, LY171555 (quinpirole). A three compartment apparatus was used: the animals' pre-experimental preference for the two choice compartments was equal and, within each experimental group, half the rats received drug pairings in each choice compartment. Intraperitoneal injections of SKF38393 produced conditioned place aversions at all doses tested (1.0-4.0 mg/kg); LY171555 produced weak conditioned place preferences at 1.0 and 2.0 mg/kg, but no reliable effect at 4.0 mg/kg. Bilateral intra-accumbens microinjections of SKF38393 produced strong preferences at all doses tested (0.5-2.0 micrograms/side); LY171555 produced strong preferences at two doses (0.5 and 1.0 micrograms/side) and no effect at a third dose (2.0 micrograms/side). These results suggest that activation of either D1 or D2 receptors in the nucleus accumbens can produce reward, and that D1 receptors (and possibly also D2 receptors) located elsewhere in the brain or in the periphery may mediate aversive effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Localized intracaudate dopamine D2 receptor activation during the post-training period improves memory for visual or olfactory conditioned emotional responses in rats.

Rats with cannulas aimed at the posteroventral (PV) or ventrolateral (VL) areas of the caudate nucleus were trained on a conditioned emotional response (CER) task. Post-training microinjections of the indirect catecholamine agonist, d-amphetamine (5 micrograms), or of the dopamine D2 receptor agonist, LY171555 (1 microgram), into the PV area improved retention of a CER with a visual CS, but had no effect on a CER with an olfactory CS. Post-training injections of the same two drugs into the VL area improved retention of a CER with an olfactory CS, but had no effect on a CER with a visual CS. Post-training injections of the dopamine D1 receptor agonist, SKF38393 (0.5, 1.0, 2.0 micrograms), into either site had no effects on either CER. These findings suggest that different areas of the caudate nucleus mediate acquisition of CERs with different CSs, possibly implicating the topographically organized corticostriatal innervation in the acquisition of certain types of memories in the caudate nucleus. The findings also suggest that dopamine D2 receptors in the caudate nucleus are involved in the acquisition of these CERs.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Dissociation of hippocampus and caudate nucleus memory systems by posttraining intracerebral injection of dopamine agonists.

The effect of posttraining intracerebral injections of the indirect dopamine (DA) agonist d-amphetamine, the direct D2 agonist LY 171555, and the direct D1 agonist SKF-38393 on the acquisition of two 8-arm radial maze tasks were examined. On a win-stay task, a light cue signaled the location of food in 4 randomly selected maze arms on each trial, and animals were required to visit each of the lit arms twice within a trial. Posttraining intracaudate injection of d-amphetamine (10.0 and 15.0 micrograms), LY 171555 (2.0 micrograms), and SKF-38393 (5.0 micrograms) all improved win-stay acquisition in relation to saline-injected controls. In contrast, posttraining intrahippocampal injection of DA agonists had no effect on win-stay acquisition. On a win-shift task, rats were allowed to obtain food from 4 randomly selected maze arms, followed by a delay period in which they were removed from the maze. They were returned to the maze for a retention test in which only those arms that had not been visited before the delay contained food. Posttraining intrahippocampal (but not intracaudate) injection of d-amphetamine (5.0 micrograms), LY 171555 (2.0 micrograms), and SKF-38393 (5.0 micrograms) all improved win-shift retention in relation to saline-injected controls. The results demonstrate a double dissociation of hippocampus and caudate nucleus memory functions and show that posttraining injection of both D1 and D2 agonists modulate the memory processes subserved by both hippocampus and caudate nucleus.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

The lateral nucleus of the amygdala mediates expression of the amphetamine-produced conditioned place preference.

We investigated the involvement of the hippocampal formation and the amygdala in the acquisition and expression of the amphetamine-produced conditioned place preference (CPP). Animals were conditioned in four sessions that included two pairings of d-amphetamine (2.0 mg/kg, s.c.) with one of two distinct compartments and two pairings of vehicle with the other compartment in a counterbalanced manner. Animals' preferences for the compartments were then tested in the absence of amphetamine. The CPP was attenuated by preconditioning electrolytic or excitotoxic lesions of the lateral nucleus of amygdala, but not by electrolytic lesions of the central or basolateral nucleus of amygdala, endopiriform nucleus, or ventral hippocampus or by radio-frequency lesions of the fornix-fimbria. When the lateral nucleus of amygdala was damaged by electrolytic or excitotoxic lesions after conditioning, animals failed to express an amphetamine-produced CPP. These results demonstrate that expression of the amphetamine-produced CPP is mediated by intrinsic neurons of the lateral nucleus of the amygdala, and that neither acquisition nor expression of the CPP is mediated by the central or basolateral amygdaloid nucleus or the hippocampus-accumbens projection. Combined with our previous finding that the expression of the amphetamine-produced CPP is also mediated by dopamine receptor activation in the nucleus accumbens (Hiroi and White, 1989, 1990), it could be suggested that the lateral nucleus of the amygdala and dopamine terminals in the nucleus accumbens are parts of the neural circuitry that mediates the expression of the amphetamine-produced CPP.

Amphetamine↗
PubMed1990

Post-training injection of the acetylcholine M2 receptor antagonist AF-DX 116 improves memory.

The present study examined the effect of systemic post-training administration of the acetylcholine muscarinic M2 receptor antagonist AF-DX 116 on the acquisition of two 8-arm radial maze tasks. On a win-stay visual discrimination task, a light cue signalled the location of food in 4 randomly selected maze arms, and rats were required to visit each of the 4 lit arms twice within a trial. Rats were given one trial per day and injected immediately post-training on day 5. AF-DX 116 (0.5 and 1.0 mg/kg) significantly improved win-stay acquisition relative to vehicle-injected controls. On a win-shift task, rats were allowed to visit 4 randomly selected maze arms, followed by a delay period. After the delay, rats were returned to the maze for a retention test in which only those 4 arms not visited prior to the delay contained food. On the test (i.e. drug) trial, rats were removed from the maze after the first 4 choices and injected with AF-DX 116 or vehicle. The retention test was given following an 18 h delay. AF-DX 116 (2.0 mg/kg) significantly improved retention relative to vehicle controls. When the injections were given 2 h post-training, no effect on retention was observed in either task. The results demonstrate that post-training injection of the selective M2 receptor antagonist AF-DX 116 improves memory in a time-dependent manner. The findings may have implications for the cholinergic pharmacotherapy of Alzheimer's disease.

Animals↗
PubMed1990

The reserpine-sensitive dopamine pool mediates (+)-amphetamine-conditioned reward in the place preference paradigm.

The neural basis of amphetamine-conditioned reward was investigated in the conditioned place preference paradigm. When bilaterally injected into the nucleus accumbens before the test session, a dopamine receptor blocker, alpha-flupenthixol, blocked the expression of the amphetamine-conditioned place preference. alpha-Flupenthixol had no significant effect on spontaneous locomotor activity. Bilateral microinjections of a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (alpha-MPT), decreased (+)-amphetamine locomotor stimulation in a dose-dependent fashion. Two doses of alpha-MPT that completely blocked (+)-amphetamine locomotor stimulation had no effect on the expression of the conditioned place preference when injected into the nucleus accumbens before testing. Reserpine administered subcutaneously before testing blocked the expression of the conditioned place preference. A dose of reserpine (4.0 mg/kg), which completely blocked the conditioned place preference, did not attenuate (+)-amphetamine-induced locomotor stimulation. This dose of reserpine depleted dopamine in the nucleus accumbens to 4% of its normal value. These data show that (+)-amphetamine-conditioned reward, expressed as a conditioned place preference, is mediated by dopamine release in the nucleus accumbens. Moreover, the dopamine is released from the reserpine sensitive pool, and probably not from the newly synthesized alpha-MPT-sensitive pool.

Amphetamines↗