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Donald W Pfaff

Publications and source records attributed to Donald W Pfaff.

45 records · Page 3Linked to original sources
PubMed2002

Reversal of sex differences in morphine analgesia elicited from the ventrolateral periaqueductal gray in rats by neonatal hormone manipulations.

Male rats display significantly greater analgesic responses than female rats following systemic, ventricular and intracerebral morphine administration into either the ventrolateral periaqueductal gray (vlPAG) or the rostral ventromedial medulla, and following beta-endorphin administration into the vlPAG. Although adult gonadectomy severely reduces nonopioid forms of swim stress-induced analgesia, the marked sex differences in morphine analgesia were minimally affected by either male or female adult gonadectomy. Since very little is known about neonatal effects of gonadal hormones upon sex differences in morphine analgesia elicited from the vlPAG, the present study evaluated the effects of neonatal (within 1 day of birth) castration in male rat pups relative to sham-operated controls, and systemic androgenization with testosterone propionate in female rat pups relative to vehicle-injected controls upon baseline nociceptive thresholds and morphine analgesia elicited from the vlPAG in rats tested as adults. Significant sex differences in morphine analgesia elicited from the vlPAG were observed with adult males receiving neonatal sham surgeries displaying significantly greater morphine analgesia on two nociceptive measures than adult females tested during the estrous phase and receiving neonatal vehicle injections. Neonatal gonadectomy essentially reversed the pattern of sex difference effects upon morphine analgesia elicited from the vlPAG. Neonatally-castrated male rats tested in adulthood displayed dramatic reductions in morphine analgesia elicited from the vlPAG on both the tail-flick (approximately 15-fold rightward shift) and jump (6-fold rightward shift) tests relative to sham-operated males, and essentially mirrored those of vehicle-treated females. Conversely, neonatally-androgenized female rats tested in adulthood displayed dramatic increases in morphine analgesia elicited from the vlPAG on the tail-flick (5-fold leftward shift) and jump (12-fold leftward shift) tests relative to vehicle-treated females, and approximated those observed in sham-operated males. The potent differences between neonatally-castrated and sham-operated male rats and between neonatally-androgenized and vehicle-treated female rats suggest a possible 'organizational' role of gonadal hormones in mediating sex differences in morphine analgesia elicited from the vlPAG.

Analgesics, Opioid↗
PubMed2002

Attentional phenotypes for the analysis of higher mental function.

We outline a strategy to relate normal cognitive processes to candidate genes. First, brain imaging is used to specify a cognitive process "attention" in terms of the neural networks involved. Next, evidence is presented showing that the operation of each network involves a dominant neuromodulator. Then we discuss development of a task designed to measure the efficiency of each network in normal individuals and consider evidence on the independence, reliability, and heritability of the networks. DNA from cheek swabs of subjects who performed the task are then used to examine candidate polymorphisms in genes related to the transmitters. We then examine the ability of these candidate alleles to predict the efficiency of relevant networks. This process has demonstrated that candidate genes are related to specific networks of attention to a greater degree than to overall performance as measured by reaction time and accuracy. These findings require replication and possible extension to other cognitive processes.

Analysis of Variance↗
PubMed2002

Genotype/age interactions on aggressive behavior in gonadally intact estrogen receptor beta knockout (betaERKO) male mice.

Estrogen, as an aromatized metabolite of testosterone, has a facilitatory effect on male aggressive behavior in mice. Two subtypes of estrogen receptors, alpha (ER-alpha) and beta (ER-beta), in the brain are known to bind estrogen. Previous studies revealed that the lack of ER-alpha gene severely reduced the induction of male aggressive behavior. In contrast, mice that lacked the ER-beta gene tended to be more aggressive than wild type (WT) control mice, although the behavioral effects of ER-beta gene disruption were dependent on their social experience. These findings lead us to hypothesize that estrogen may facilitate aggression via ER-alpha whereas it may inhibit aggression via ER-beta. In the present study, we further investigated the role of ER-beta in the regulation of aggressive behavior by examining developmental changes starting at the time of first onset, around the age of puberty. Aggressive behaviors of ER-beta gene knockout (betaERKO) mice were examined in three different age groups, puberty, young-adult, and adult. Each mouse was tested every other day for three times in a resident-intruder paradigm against olfactory bulbectomized intruder mice and their trunk blood was collected for measurements of serum testosterone after the completion of the study. Overall, betaERKO mice were significantly more aggressive than WT. These genotype differences were more pronounced in puberty and young adult age groups, but not apparent in the adult age group, in which betaERKO mice were less aggressive than those in two younger age groups. Serum testosterone levels of betaERKO mice were significantly higher than those of WT mice only in the pubertal age group, but not in young adult (when betaERKO mice were still significantly more aggressive than WT mice) and adult (when no genotype differences in aggression were found) age groups. These results suggest that ER-beta mediated actions of gonadal steroids may more profoundly be involved in the inhibitory regulation of aggressive behavior in pubertal and young adult mice.

Age Factors↗
PubMed2002

Temporal and spatial quantitation of nesting and mating behaviors among mice housed in a semi-natural environment.

Enhanced behavioral complexity may be observed when animals are tested in naturalistic environments and engaging in nonforced social interactions. For each of six experimental runs, different groups of five adult Swiss-Webster mice (four ovariectomized females and a single male) were maintained under 12h dark:12h light in a 122 x 122 x 30.5-cm open box containing six peripheral "nestboxes." On Day 1, females were released into the box first and their nesting behavior was observed. Two days later, each female was injected with estradiol benzoate and the male was introduced into the environment. Females were injected with progesterone (P) 48 h later and the animals were observed for an additional 14 h. Behaviors were recorded with a video camera suspended over the apparatus. Mating occurred only post-P and males always mated preferentially with certain females. The amount of nesting behavior per female on Day 1 correlated significantly with the number of times each female was mated by the male (r = 0.57, P < 0.005). In all but one run, the male ejaculated with the female who performed the most nesting behavior. While 63% of mating was in the open, 56% of nestbox matings resulted in female postmating darting to alternate nestboxes; in 19% of these cases, the female quickly returned to the mating nestbox and was mated there again. Direct approaches by females to the male and behaviors which affect pacing were observed. These behaviors have not been reported previously for mice and may provide additional endpoints for the exploration of hormonal and genetic influences on reproductive behaviors.

Animals↗
PubMed2002

Gender comparisons of control of breathing and metabolism in conscious mice exposed to cold.

We evaluated the effects of 2 h of warm (24 degrees C) and cold (6 degrees C) exposure on metabolism and ventilation (V(E)) in conscious male and female Harlan ICR Swiss Webster mice exposed to air, and 8% O(2) in N(2) (hypoxia) and to 5% CO(2) in O(2) (hypercapnia) for 2 min each at both temperatures. All cold-exposed mice increased O(2) consumption (V(O2)), and maintained body temperature. Cold-exposed females doubled their tidal volume, increased their V(E) fivefold, and doubled their ventilatory equivalent to V(O2) (V(E)/V(O2)). In contrast, cold-exposed males decreased tidal volume and doubled V(E) relative to warm exposure. The ventilatory equivalent of males was similar during warm and cold exposure. During warm exposure, mice of both genders increased their ventilatory responses to both hypoxia and to hypercapnia by different mechanisms. In contrast, during cold exposure, these responses were blunted relative to air measurements in females and decreased below air values in males. Thus, cold exposure was able to elicit gender-specific ventilatory and metabolic responses.

Animals↗
PubMed2002

Perspective: micoarrays and differential display PCR-tools for studying transcript levels of genes in neuroendocrine systems.

A central goal of neuroendocrinology is the understanding of how hormones modulate a variety of neurobiological functions including releasing factors for anterior pituitary secretions and behavior. We know that mechanisms of hormone actions clearly include the activation and repression of genes either directly through nuclear hormone receptors or indirectly, through a series of transduced signals originating from membrane receptors. Until recently, identification of the differentially expressed genes has been a "gene-at-a-time" proposition. With the advent of the completion of sequencing of several genomes including those of the human and mouse, new methods for the simultaneous assessment of many genes' expression are proving especially timely. Two such methods, differential display PCR and gene microarrays, are based on the well-established principles of DNA amplification and nucleic acid hybridization, respectively. With properly designed and well-executed experiments, these methods are powerful tools in the assessment of differentially expressed genes yielding results both expected and unanticipated.

Animals↗
PubMed1984

Analgesia after lesions of nucleus reticularis magnocellularis: differential effect on supraspinal versus spinal pain reflexes.

The present studies examine the effect of bilateral electrolytic lesions of descending fibers arising from nucleus reticularis magnocellularis (NMC) on responding to noxious peripheral thermal or mechanical stimulation and on spinal cord monoamine levels. The lesion effects were quantified by examining two supraspinally organized pain responses, the hot plate latency and vocalization threshold and two spinally organized nociceptive reflexes, tail flick latency and hind limb flexion threshold. Following interruption of descending NMC fibers, a profound analgesia was observed on supraspinally organized pain responses. Assay of spinal cord serotonin (5-HT) indicated that the NMC lesions also destroyed appreciable numbers of descending 5-HT fibers of passage originating in nucleus raphe magnus (RM). A modest hypersensitivity to pain occurred after control lesions in RM suggesting that the analgesia observed after NMC lesions would have been even more pronounced if RM fibers of passage had not been concomitantly destroyed. To assess whether the analgesia observed after NMC lesions was due to non-specific destruction of a given volume of reticular tissue, control lesions were placed in nucleus subcoeruleus (NSC). NSC lesions resulted in a hypersensitivity to pain and significant depletion of spinal cord noradrenaline (NA). These data suggest both that the analgesia observed after NMC lesions was not due to non-specific destruction of the reticular formation, and that descending NSC NA fibers tonically suppress pain. The above analgesic effects were observed exclusively on supraspinally organized pain responses, not spinally organized nociceptive reflexes. This supported previous studies demonstrating differential descending control of nociception in the spinal versus intact preparations. In summary, the present data suggest that descending NMC fibers tonically suppress ascending pain transmission.

Analgesia↗
PubMedDate not supplied

Hormonal and genetic influences underlying arousal as it drives sex and aggression in animal and human brains.

Estrogen treatment induces transcription and increases excitability and reproductive behavior. Estrogens provide the structural basis for increased synaptic activity and greater behavior-facilitating output. Administration of progesterone amplifies the effect of estrogens on mating behavior. The role of GnRH is to synchronize reproductive behavior with the ovulatory surge of LH. A causal connection can be charted from one individual gene to human social behavior, but only via six causal links. Glia, meninges and neurons may participate, under the influence of sex hormones, in the direction of sex behavior. Neural and genetic mechanisms for motivation may lead to biological understanding of functions that apply to the most primitive aspects of human mental functioning. With respect to aggression, besides testosterone and its metabolites, serotonergic projections to the forebrain play an important role.

Aggression↗