George S. Borszcz

Potentiated Startle: Its Relation to Freezing and Shock Intensity in Rats

Acoustic startle response and freezing were measured in a potentiated startle paradigm in which a startle stimulus was presented either alone or in the presence of a light conditioned stimulus (CS) which 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 Davis and Astrachans (1978) study. However, rather than suppressing startle, as they suggested, freezing facilitated startle and, like startle amplitude, was nonmonotonically related to shock intensity. Experiment 2 replicated these results and showed a regularly decreasing monotonic extinction function for potentiated startle and shock-associated freezing for both shock-level groups. Brown, Kalish, and Farber (1951) reported that the magnitude of the acoustic startle response was increased when the startle-eliciting stimulus was presented in conjunction with a stimulus previously paired with shock. This phenomenon, now commonly called the potentiated startle effect, has been frequently

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.

Comparison of motor reflex and vocalization thresholds following systematically administered morphine, fentanyl, and diazepam in the rat: Assessment of sensory and performance variables

The relative influence of systemically administered morphine, fentanyl, and diazepam on the thresholds of spinal motor reflexes (SMRs), vocalizations elicited during stimulation (VDSs), and vocalization afterdischarges (VADs) was assessed. Responses were elicited by applying graded electric current to the tail. Performance (latency and amplitude) of all three responses was monitored to determine whether elevations in threshold were confounded by performance decrements. All three drugs were found to elevate VAD thresholds more readily than VDS and SMR thresholds. VADs were also most susceptible to the deleterious effects of these drugs on motor performance. Nevertheless, across the dose range of morphine and fentanyl that elevated thresholds of all three responses without disrupting the performance of any response, the order of susceptibility to threshold increases remained VAD, VDS, and SMR. Diazepam also elevated VAD thresholds more readily than VDS thresholds across a dose range that failed to disrupt performance of either response. SMR thresholds were only elevated by diazepam when administered in doses that significantly disrupted performance. Results are discussed in terms of supporting the validity of VADs as a model of the affective-motivational dimension of pain.

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 raphé 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 after discharges, VADs) levels of the neuraxis was assessed. Dose-dependent increases in response thresholds differed with the site of morphine injection. These results indicate that the mu-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.

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

Unconditional responses (URs) of the rat that predict 1-trial, step-through passive avoidance conditioning were identified. The URs examined were spinal motor reflexes (SMRs) and vocalization afterdischarges (VADs) generated by tailshock. In Experiment 1, SMR and VAD thresholds were determined following systemic administration of saline or morphine sulfate. Experiment 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 deficts or its induction of state-dependent learning (Experiment 3). The results are consistent with the 2-process theories of J. Konorski (1967) and A. R. Wagner & S. E. Brandon (1989) in which the unconditional stimulus is viewed as being composed of separable but interrelated epicritic-sensory and protopathic-emotive attributes.

Characterization of tailshock elicited withdrawal reflexes in intact and spinal rats

The tail flick withdrawal reflex (TFR) was generated by applying graded electric current to the tail of intact and spinally transected rats. In Experiment 1, separate groups of rats were tested 1, 3, 7, 10, 14, or 21 days after spinal transection. The latency, amplitude, and magnitude of the TFR was highly related to current intensity in both intact and spinal animals. However, the TFR changed dramatically as a function of the number of days between spinalization and TFR measurement. Compared to intact controls, the current intensity at which TFR was initiated (threshold) in spinal rats was elevated 1 and 3 days after transection, did not differ at 7 and 10 days, and was reduced at 14 and 21 days. Latency of TFR in spinal rats did not differ from controls 1 day after transection, but decreased steadily thereafter. Amplitude and magnitude of TFR in spinal rats remained depressed, but did show recovery toward control levels as the interval between transection and testing increased. Changes in the TFR of spinal rats was correlated with recovery of tailpinch-elicited hindlimb withdrawal. Experiment 2 demonstrated that the dose-response curve relating systemic morphine treatment to increases in TFR thresholds was shifted to the right in chronic spinal rats. Threshold increases in both spinal and intact rats were not necessarily accompanied by changes in TFR performance. These experiments establish the segmental organization of tailshock-elicited TFR and supports its use as a measure of nociceptive transmission at spinal levels.

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.

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 mu-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.

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 microg, 5 microg, and 10 microg) 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.

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 afterdischarges (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 micrograms and 1 microgram 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.