Differential contributions of medullary, thalamic, and amygdaloid serotonin to the antinociceptive action of morphine administered into the periaqueductal gray: A model of morphine analgesia.

The relative contribution of serotonin (5HT) neurotransmission within the medulla (rostral ventromedial medulla) and forebrain (amygdaloid central nucleus and nucleus parafascicularis thalami) to the antinociceptive action of morphine microinjected into the ventrolateral periaqueductal gray (vPAG) was evaluated. The 5HT receptor antagonist methysergide was microinjected into the medulla, forebrain, (or both) after injection of morphine into the vPAG. The contribution of 5HT to the antinociceptive action of morphine was observed to depend on (a) the dose of morphine administered into the vPAG, (b) the site(s) at which methysergide was administered, and (c) the level of the neuraxis at which the behavioral assay was organized. Results of the present study were combined with those of previous studies from this laboratory and presented as a model of the mechanisms by which morphine administered into the vPAG generates its antinociceptive action. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increases in vocalization and motor reflex thresholds are influenced by the site of morphine microinjection: Comparisons following administration into the periaqueductal gray, ventral medulla, and spinal subarachnoid space.

The relative influence of morphine microinjected into the periaqueductal gray, ventral medulla (nucleus raphe magnus or nucleus reticularis gigantocellularis), or spinal subarachnoid space on the thresholds of responses organized at spinal (spinal motor reflexes, SMRs), medullary (vocalizations elicited during shock, VDSs), and rhinencephalic-diencephalic (vocalization afterdischarges, VADs) levels of the neuraxis was assessed. Dose-dependent increases in response thresholds differed with the site of morphine injection. These results indicate that μ opiate receptor-linked systems in the mesencephalon, medulla, and spinal cord exert differential antinociceptive effects on pain behaviors organized at different levels of the neuraxis. A hypothesis is offered regarding the mechanisms through which morphine inhibits nociceptive transmission through various levels of the CNS. VADs are promoted as a model system for analyzing the affective-motivational dimension of the pain experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The differential contribution of spinopetal projections to increases in vocalization and motor reflex thresholds generated by the microinjection of morphine into the periaqueductal gray.

The capacity of morphine microinjected into the ventrolateral periaqueductal gray (vPAG) to elevate the thresholds of spinal motor reflexes (SMRs), vocalizations during shock (VDSs) and vocalization afterdischarges (VADs) was challenged by the intrathecal administration of receptor antagonists to serotonin (methysergide), norepinephrine (phentolamine) and μ-opiates (naloxone). Methysergide and phentolamine were equipotent in reversing increases in SMR thresholds. The efficacy of these antagonists to reduce increases in VDS and VAD thresholds was dependent on the dose of morphine administered into the vPAG. These results indicate that the dose of morphine administered into the vPAG determines the contribution of spinopetal projections in inhibiting dorsal horn neurons involved in reflex generation versus the rostral transmission of pain information. A hypothesis is offered regarding the mechanisms by which vPAG administered morphine suppresses nociceptive transmission through different levels of the neuraxis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Short-term and long-term habituation of the acoustic startle response in chronic decerebrate rats.

13 chronic decerebrate male albino rats, maintained in good condition for 31–84 postoperative days, showed significant within-session habituation of the acoustic startle response. However, they showed no habituation over days under conditions that produced significant response deficits in controls. The decerebrates' stimulus-provoked response deficits may have endured for up to 40 min between sessions, and they were apparently more than normally susceptible to stimulus-provoked sensitization. Data are consistent with models that assume that the mechanisms for short-term habituation are intrinsic to the stimulus-response (S–R) pathway in the lower brain stem. On the other hand, relatively permanent long-term habituation of the acoustic startle response must be mediated by extrinsic mechanisms rostral to the S–R pathway that superimpose an inhibitory influence on that pathway. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increases in vocalization and motor reflex thresholds generated by the intrathecal administration of serotonin or norepinephrine.

The capacity of serotonin and norepinephrine to elevate the thresholds of spinal motor reflexes (SMRs), vocalizations during shock (VDSs), and vocalization aftcrdischarges (VADs) when administered into the spinal subarachnoid space was evaluated. Both monoamines generated dose-dependent increases in the thresholds of all 3 responses. The minimum effective doses of serotonin and norepinephrine that elevated all 3 response thresholds were 40 μg and 1 μg, respectively. Monoamine-induced increases in response thresholds were reversed by the intrathecal administration of their corresponding receptor antagonists (phentolamine or methysergide). Threshold increases generated by serotonin were also partially reduced by phentolamine. These results indicate that dorsal horn neurons that underlie flexion reflex generation (SMR) and the rostral transmission of pain information (VDS and VAD) have similar thresholds of inhibition to spinopetal monoaminergic projections. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The capacity of motor reflex and vocalization thresholds to support avoidance conditioning in the rat.

Unconditioned responses (UCRs) of the rat that predict 1-trial, step-through passive avoidance conditioning were identified. The UCRs examined were spinal motor reflexes (SMRs) and vocalization aftercharges (VADs) generated by tailshock. In Exp 1, SMR and VAD thresholds were determined following systemic administration of saline or morphine sulfate. Exp 2 revealed that the capacity of these tailshocks to support conditioning covaried with the probability that VADs were elicited and were independent of the proportion of SMRs that were generated. This pattern of conditioning was not a consequence of either morphine-induced memory deficits or its induction of state-dependent learning (Exp 3). The results are consistent with the 2-process theories of J. Konorski (1967) and A. R. Wagner and S. E. Brandon (1989) in which the unconditional stimulus is viewed as being composed of separate but interrelated epicritic–sensory and protopathic–emotive attributes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiated startle: Its relation to freezing and shock intensity in rats.

Two experiments with 47 albino rats measured acoustic startle response and freezing in a potentiated startle paradigm in which a startle stimulus was presented either alone or in the presence of a light conditioned stimulus/stimuli (CS) that had been paired previously with either 1-mA or 3-mA footshock. During the CS, the 1-mA group had higher startle amplitudes and a higher percentage of freezing than the 3-mA group. Startle amplitude was positively correlated with freezing under all conditions. The nonmonotonic relation between potentiated startle and shock intensity replicated the study of M. Davis and D. I. Astrachan (see record 1979-00353-001). However, rather than suppressing startle, as they suggested, freezing facilitated startle and, like startle amplitude, was nonmonotonically related to shock intensity. In Exp II, these results were replicated and showed a regularly decreasing monotonic extinction function or potentiated startle and shock-associated freezing for both shock-level groups. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pavlovian conditional vocalizations of the rat: A model system for analyzing the fear of pain.

Presentation of a 6-s light conditional stimulus (CS) that overlapped with a 1-s tailshock unconditional stimulus (US) generated audible conditional vocalization responses (VCRs) during the CS period. The rate of conditioning was observed to be directly related to the intensity of the tailshock US (0.15 mA-0.80 mA). The amplitude, duration, and number of VCRs was also directly related to US intensity, whereas the latency of VCRs from CS onset was inversely related to US intensity. VCRs were not observed in rats given explicitly unpaired presentations of CS and US (0.80 mA). The capacity of tailshock to support development of VCRs was found to depend on its capacity to elicit vocalization afterdischarges (VADs). Sonographic analysis of vocalizations revealed that VCRs and VADs share spectrographic characteristics. Results are discussed in terms of VCRs' providing a model system for analyzing the fear of pain and its suppression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of long-term sensitization on long-term habituation of the acoustic startle response in rats: Central gray lesions, preexposure, and extinction.

The relation between long-term decrements of the acoustic startle response in rats and the development of freezing behavior during habituation training was examined. Freezing behavior developed over the initial trials of habituation training, and the rate of long-term response decrements was found to be inversely related to the development of freezing. Manipulations (neurological or behavioral) that either reduced the level of freezing or retarded its development promoted startle response decrements. In Experiment 1, rats receiving electrolytic lesions of the ventrolateral periaqueductal gray demonstrated both accelerated long-term startle response decrements and retarded development of freezing behavior. In Experiment 2, preexposure to the startle apparatus (i.e., latent inhibition) accelerated long-term startle decrements and inhibited development of freezing. In Experiment 3, exposure to the startle apparatus following initial habituation training (i.e., extinction) reduced both freezing behavior and startle response amplitudes. The results are discussed in terms of the influence of Pavlovian fear conditioning on long-term habituation of the acoustic startle response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amygdaloid–thalamic interactions mediate the antinociceptive action of morphine microinjected into the periaqueductal gray.

The bilateral administration of the serotonin receptor antagonist methysergide (2.5 μg, 5 μg, and 10 μg) into either the central nucleus of the amygdala (ACe) or nucleus parafascicularis thalami (nPf) produced dose-dependent inhibition of the antinociceptive action of ventrolateral periaqueductal gray (vPAG)-administered morphine. Unilateral administration of these doses of methysergide into either the ACe or nPf had no effect on morphine-induced antinociception. However, the combined unilateral administration of these doses of methysergide into the ACe and nPf produced dose-dependent inhibition of morphine antinociception that was identical to that observed after its bilateral administration into either site. This latter finding is interpreted as evidence that a functional interaction between the ACe and nPf supports the antinociceptive action of morphine administered into the vPAG. (PsycINFO Database Record (c) 2010 APA, all rights reserved)