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Biomedical subjects

A G Phillips

Publications and source records attributed to A G Phillips.

At least 163 records · Page 9Linked to original sources
PubMed1977

Monoamine involvement in hippocampal self-stimulation.

The roles of noradrenergic and serotonergic projections to the hippocampus were investigated with respect to their involvement in the intracranial self-stimulation of this structure. In the first study, 6-hydroxydopamine-induced lesions of the dorsal tegmental noradrenergic bundle, which depleted hippocampal NE by 97%, had no effect on hippocampal self-stimulation in rats. In the second study, intragastric administration of para-chlorophenylalanine (PCPA) decreased hippocampal self-stimulation, suggesting the importance of a serotonin input in maintaining this behavior. Identical PCPA treatments resulted in temporary depletions of brain serotonin which paralleled the changes in hippocampal self-stimulation. The maximal decreases in both the biochemical and behavioral measures occured at 4 days post-drug. Interpretations of this deficit in hippocampal self-stimulation in terms of gross sensory and/or motor changes were ruled out as animals with lateral hypothalamic electrodes showed increases in self-stimulation paralleling the post-drug serotonin changes. An intra-sessional analysis of the PCPA-induced behavioral changes revealed that lateral hypothalamic self-stimulation was facilitated mainly during the first hour of the two-hour test sessions, whereas the depression in hippocampal self-stimulation occurred primarily in the last hour of the sessions. The differential effects of PCPA on lateral hypothalamic and hippocampal self-stimulation provide evidence against simple monoamine theories of reinforcement.

Animals↗
PubMed1977

Trigeminal substrates of intracranial self-stimulation in the brainstem.

Intracranial self-stimulation was elicited by electrodes located in the trigeminal motor nucleus of the rat. Rebound jaw movements were also elicited at postiive self-stimulation placements, but control experiments revealed that the lever pressing was not a motor artifact. It is suggested the modulation of trigeminal motoneurons may serve as an important reinforcement mechanism in the brainstem.

Animals↗
PubMed1977

Effects of chlordiazepoxide on tail pinch-induced eating in rats.

The effects of 5, 10, and 20 mg/kg chlordiazepoxide on tail pinch (TP)-induced behavior were investigated. Five mg/kg enhanced TP-induced eating in terms of both latency and duration. Twenty mg/kg had decremental effects. All doses of the drug reduced the incidence of clip-directed behavior, but increased locomotor activity during the TP trials in a dose-dependent manner. On control trials, the drug increased locomotor activity at the low dose and eating at the high dose. The results are examined in terms of the various behavioral actions of the minor tranquilizers. The implications for the behavioral and neuropharmacological mechanisms underlying TP-induced and other forms of stimulus-bound behavior are discussed.

Animals↗
PubMed1977

Temporal analysis of naloxone attenuation of morphine-induced taste aversion.

In a dose-response study, 7.5 mg/kg of naloxone produced maximal attenuation of conditioned taste aversion to saccharin induced by 10 mg/kg of morphine. Naloxone was administered immediately after the morphine in this study. In a second experiment, naloxone still caused a significant attenuation of taste aversions when administered with a 1 hr delay after morphine, but not after delays of 4 or 8 hr. These results suggest that behavioral consequences of morphine which peak during the first hr after injection (analgesia, catalepsy, and depression of intracranial self-stimulation) are not correlated with the aversive effect of morphine. Nor can the aversiveness of morphine be attributed to withdrawal effects. Only the facilitative actions of morphine occurring 1 to 4 hr after injection, including the facilitation of intracranial self-stimulation, are temporally correlated with the naloxone-sensitive aversive effect. Thus, a temporal analysis cannot be used to dissociate the paradoxical positive reinforcement and aversive effects of morphine. Rather, the temporal correlation between the two opposite motivational effects of morphine serves to emphasize the nature of this paradox.

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PubMed1976

Retrograde amnesia after electrical stimulation of the substantia nigra: mediation by the dopaminergic nigroneostriatal bundle.

Stimulation of the zona compacta of the substantia nigra (SNC) has been reported to impair the long-term retention of a passive avoidance step-down task. In the present experiments it was observed that previous ipsilateral lesions of the dopaminergic nigro-neostriatal bundle (NSB) with 6-hydroxydopamine blocked the stimulation-induced memory deficit. Unilateral or bilateral lesions of the dopaminergic NSB did not by themselves disrupt acquisition or retention of the passive avoidance task. In addition, the memory deficit observed after electrical stimulation of the caudate-putamen was not reduced by ipsilateral NSB lesions. These results indicate that the retention deficit produced by stimulation of the SNC was mediated by the dopaminergic NSB. However, in view of the fact that lesions of this projection did not affect acquisition or retention of the step-down task, it is suggested that this system is not critically involved in learning and memory. Rather, it is hypothesized that stimulation of the SNC results in an excess release of dopamine in the caudateputamen which interferes with neurochemical and neurophysiological events in this structure which are important substrates for long-term memory.

Amnesia↗
PubMed1976

Differential effects of para-chlorophenylalanine on self-stimulation in caudate-putamen and lateral hypothalamus.

Rats were prepared with chronic bipolar electrodes aimed at either the caudate-putamen or lateral hypothalamus and those displaying consistent self-stimulation were given additional training at half-maximal current intensities. All subjects received an intragastric injection of para-chlorophenylalanine (400 mg/kg) and self-stimulation tests continued until pre-injection rates were re-established. Responding in both brain areas was suppressed 24 h after drug treatment. The next day, self-stimulation rates in the hypothalamus increased to 115% of pre-drug levels reaching a level of 180% by the third day of post-drug testing. In contrast, self-stimulation of sites in the neostriatum continued to decline, with minimal levels reaching 48% of control on the fourth post-drug day. Self-stimulation rates in both groups had returned to control levels by post-drug day 6. These data indicate that the role of serotonergic mechanisms in brain stimulation is locus specific, and that the specific nature of this role may be determined by interaction with other neurochemical systems. The possible interaction between dopaminergic and serotinergic mechanisms in the neostriatum is discussed as a model of self-stimulation in this region of the brain.

Animals↗
PubMed1976

Evidence that self-stimulation of the region of the locus coeruleus in rats does not depend upon noradrenergic projections to telencephalon.

Rats with intracranial self-stimulation (ICSS) electrodes in the locus coeruleus and adjacent pontine tegmental structures received stereotaxically placed bilateral injections of 6-hydroxydopamine (4 mug/2 mul) into the mesencephalic trajectory of the dorsal tegmental noradrenergic bundle. The consequent depletions of norepinephrine in the cerebral cortices and hippocampi (96.7%) did not result in significant changes in ICSS. Thus, diencephalic and telencephalic noradrenergic projections of the locus coeruleus do not appear to be critical for the occurrence of ICSS from that nucleus or its surrounding region. Nor do these projections appear to be crucially involved in the enhancement of this ICSS by D-amphetamine. Rats in this study showed two-fold increases in responding following injections of D-amphetamine sulfate (0.5 mg/kg) both before and after the lesions of the dorsal tegmental bundle. These results suggest that the ascending projections of the locus coeruleus are not critically involved in ICSS of the dorsal pontine tegmentum.

Animals↗
PubMed1976

Decreased intracranial self-stimulation after neuroleptics or 6-hydroxydopamine: evidence for mediation by motor deficits rather than by reduced reward.

Rats were implanted with electrodes in the lateral hypothalamus, put on a 22-h food deprivation schedule and trained to bar-press for ICS and for food on a CRF schedule. Haloperidol (0.08 mg/kg) and pimozide (0.22 mg/kg) significantly decreased responding for both reinforces, although responding for ICS was decreased more than it was for food. The same doses of these drugs did not decrease food consumption of a 15-min ad libitum test after 22-h of food deprivation, suggesting that the decreased bar-pressing for food was not the result of anorexia or reduced motivation for food. When similar rates of responding for ICS and for food were obtained on a V1 60 schedule, haloperidol (0.1 mg/kg) reduced responding for food and ICS to a similar extent. Thus, when baseline rate is controlled for, neuroleptics do not selectively reduce responding for ICS. In addition, examination of cumulative response records revealed that rather than producing an extinction curve, as would be predicted if neuroleptics reduced the rewarding properties of ICS, haloperidol produced a uniform decrease in the rate of responding throughout the experimental session. Similar results were obtained with intraventricular 6-hydroxydopamine (6-OHDA) injections. While these experiments do not exclude the possibility that dopaminergic (DA) systems participate in some central reinforcement mechanisms, they suggest that neuroleptics and 6-OHDA decrease responding for food or ICS primarily by impairing the function of DA systems critically involved in the initiation or maintenance of operant behaviour rather than by interfering with reward.

Animals↗
PubMed1976

Dopaminergic substrates of intracranial self-stimulation in the caudate-putamen.

An extensive mapping of the caudate-putamen in rat for intracranial self-stimulation (ICS) site was undertaken to provide addtional support for the role of dopamine in brain-stimulation reward. Eight-seven per cent of the placements in the neostriatum supported ICS, with self-stimulation rates greater than 250/15 min at 56% of these sites. Electrical stimulation also elicited rearing and clonus, and contralateral body turn, both of which varied in magnitude between animals. In a second experiment, animals were prepared with electrodes aimed at the lateral caudateputamen. Those subjects displaying ICS subsequently received 6-hydroxydopamine lesions to the dopamine cell bodies in the substantia nigra pars compacta, either ipsilateral or contralateral to the electrode. The destruction of the dopamine cell bodies attenuated ICS in both groups during the first post-lesion test sessions. However, the rates in the ipsilateral group declined to between 2 and 9% of control scores, whereas the rate in the contralateral group improved over testing to 72% of control values, 28 days after the lesion. On the basis of these data, it was concluded that unilateral destruction of the dopaminergic nigro-neostriatal bundle (NSB) has two effects on ICS behavior. First, unilateral reduction of neostriatal dopamine is accompanied by a loss of brain-stimulation reward at sites normally innervated by the NSB, specifically the caudate-putamen. Secondly, lesions of the NSB produce a general disruption in bar-pressing behavior, as evidenced by the attenuation of ICS following contralateral lesions.

Animals↗
PubMed1975

Effects of amphetamine isomers and neuroleptics on self-stimulation from the nucleus accumbens and dorsal noradrenergic bundle.

In an attempt to examine the possible role of noradrenergic (NA) and dopaminergic (DA) systems in intracranial self-stimulation (ICS), the rate-increasing effects of D- and L-amphetamine on ICS were determined in rats with nucleus accumbens electrodes (DA placement) or dorsal NA bundle electrodes (NA placement). The D-isomer produced a significantly greater increase in ICS than did the L-isomer in animals with dorsal NA bundle electrodes. In contrast, the amphetamine isomers were equipotent in facilitating ICS in animals with nucleus accumbens electrodes. These data, together with previous observations, suggest that there exists a correlation between equipotential effects of D- and L-amphetamine and DA electrode placements on the one hand, and prepotent effects of D-amphetamine and NA electrode placements on the other. Pimozide and haloperidol, which in low doses are thought to specifically block DA receptors, decreased ICS obtained from both DA and NA electrode placements. It is suggested that neuroleptic drugs may produce a general disruption of operant behavior and that the decrease in ICS produced by these agents does not therefore necessarily implicate dopaminergic mechanisms in the neurochemistry of reward.

Amphetamine↗
PubMed1975

Haloperidol-induced disruption of conditioned avoidance responding: attenuation by prior training or by anticholinergic drugs.

Rats injected daily with haloperidol (0.15 mg/kg) failed to acquire a one-way avoidance response over a 9 day period (10 trails/day). When these animals were subsequently tested without haloperidol, on the first drug-free day they preformed as well as animals given saline throughout the training period and significantly better than naive saline-treated animals on the first day of training. The performance of rats which were trained for two days before receiving haloperidol was only partly blocked by the drug, while animals trained for 9 days before drug administration were immune to the disruptive effects. Three anticholinergic (muscarinic) drugs, atropine (10 mg/kg), scopolamine (1 mg/kg) and benztropine (2 mg/kg) significantly reversed the effect of haloperidol on the acquisition of the nigroneostriatal projection and support the view that this system is critically involved in the acquistion of learned instrumental responses. The nature of the avoidance deficit produced by these treatments is discussed with reference to the possibility that they selectively block the initiation of boluntary motor responses. According to this hypothesis, the failure of these teratments to disrupt escape responding may be due to the fact that the unconditioned stimulus generates reflexive motor responses (flinch, jump, etc.) which are sufficient to begin the motoric sequences that cannot be initiated voluntarily in response to the conditioned stimulus.

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