Collaboration to implement smoking cessation guidelines during the childbirth continuum.

BACKGROUND: Smoking during pregnancy has been linked with such negative outcomes as increased risk for spontaneous abortions, low birth weight, and perinatal and neonatal mortality. In spring 1998 three leading health care systems in San Diego initiated the Trilateral Partnership ("the Partnership"), whose mission is to improve the health and well-being of children. The Partnership chose tobacco control in pregnant women and their families as its first initiative. PROGRAM COMPONENTS-YEAR ONE (1999): Three interventions were developed: intervention by the prenatal care provider, initiation of a referral process to telephone counseling for pregnant women, and intervention for women reporting spontaneously quitting smoking. To date, 83% of the more-than 20,000 women who have been seen in prenatal screening in 28 months counted themselves as nonsmokers. Eleven percent of the women reported they independently stopped smoking once they learned they were pregnant. Six percent reported that they were still smoking. Twenty-three percent of the women reported living in a household with other smokers. PROGRAM COMPONENTS-YEAR TWO (2000): Activity focused on continuing the previous components, hospital intervention for all new mothers at the time of delivery, pediatric intervention at the newborn's visits at 2 and 6 months of age, and development and refinement of a telephone protocol for new parents. ELEMENTS OF SUCCESS: The noncontroversial topic of encouraging smoking cessation during pregnancy was one that enhanced immediate buy-in by most individuals contacted to support and engage in the program. Strong commitment and financial support from three health care systems opened doors for the Smoke-Free Families staff and increased the program's visibility in the community.

Chronic desipramine alters stress-induced behaviors and regional expression of the immediate early gene, c-fos.

This experiment examined the effects of acute or chronic administration of the antidepressant drug desipramine on conditioned stress-induced behaviors and regional c-fos expression in the brain. To this end, rats were exposed to three sequential daily sessions of uncontrollable foot-shock and matched, on the basis of crouching, into one of four groups. Two of these groups were exposed to saline injections twice daily and two were exposed to injections of desipramine (5 mg/kg, SC) twice per day, for 9 days. On the 10th day one of the saline groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Likewise, on the 10th day one of the desipramine groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Detailed behavioral analysis showed that compared to the saline-treated controls only the group treated chronically with desipramine, including on the test day, exhibited statistically significant reductions in crouching and increases in exploration during the test session. Similarly, Fos immunohistochemistry revealed that the chronic desipramine group showing positive behavioral effects was the only group in which there were significant reductions in the number of stress-induced Fos-positive neurons in five of 60 structures surveyed. These structures included the anterior cingulate cortex, anterior claustrum, central nucleus of the amygdala, dentate gyrus of the dorsal hippocampus, and paraventricular nucleus of the thalamus. To the extent that repeated exposure to uncontrollable stress is an animal model of depression, these and previous results suggest that these structures are potentially important neural targets for the antidepressant effects of desipramine.

Acute treatment with antidepressant drugs selectively increases the expression of c-fos in the rat brain.

Rats were treated acutely, ip, with saline vehicle or an antidepressant: iprindole (15 mg/kg), nortriptyline (15 mg/kg), A75200 (10 mg/kg), fluoxetine (15 mg/kg), desipramine (10 mg/kg), bupropion (20 mg/kg) or tranylcypromine (7.5 mg/kg). Mapping the neuroanatomical distribution at 64 sites of the immediate early gene, c-fos revealed several patterns: first, increased counts of Fos-like neurons were found in all but one instance; second, drugs which had dopaminergic effects (bupropion and tranylcypromine) were more likely to potentiate c-fos reactivity than were the other drugs; third, Fos-like counts were more likely to be significantly elevated in structures bordering brain ventricles; fourth, only in the central amygdala were the Fos-like counts higher in all seven drug groups relative to the saline group. It remains to be seen whether or not this shared substrate is therapeutically significant.

Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diazepam pretreatment.

The synthesis of Fos, the protein product of the immediate early gene c-fos, was used to map metabolically some of the neural substrates of conditioned fear in the rat. Analysis of the behaviors emitted by the rats during the test session provided strong evidence that the conditioning procedure was effective. Exposure to the environment in which they had previously received footshock significantly increased the number of Fos-like immunoreactive neurons in nearly 50 brain regions, both cortical and subcortical. Among the structures showing the most dramatic increases in fear-induced c-fos expression were the cingulate, piriform, infralimbic, and retrosplenial cortices, the anterior olfactory nucleus, claustrum, endopiriform nucleus, nucleus accumbens shell, lateral septal nucleus, various amygdalar nuclei, paraventricular thalamic nucleus, ventral lateral geniculate nucleus, the ventromedial, lateral, and dorsal hypothalamic nuclei, the ventral tegmental area, and the supramammillary area. These data demonstrate that a relatively simple classical conditioning procedure activates a large number of widely dispersed cortical and subcortical structures. Some of the structures showing increased c-fos expression have important autonomic functions and may therefore have reflected centrally mediated changes in blood pressure and respiration produced by the anxiogenic stimuli. In a second experiment, the effects of pretreatment with the anxiolytic drug diazepam (2.5, 5.0, or 10 mg/kg) were evaluated. The benzodiazepine produced dose-related decreases in the frequency of crouching (freezing) elicited by the aversively conditioned contextual cues. Diazepam also produced dose-related decreases in conditioned stress-induced c-fos expression in all but one structure, the effects being statistically significant in 38 of 60 sampled structures. Diazepam dose dependently increased fear-induced c-fos expression in the central nucleus of the amygdala. There was considerable regional variability with respect to sensitivity to diazepam, the retrosplenial cortex and the supramammillary area being the only two structures to show decreases after the lowest dose of diazepam. In contrast, the entorhinal cortex, nucleus accumbens core, ventromedial and posterior hypothalamic nuclei, median raphe, and locus coeruleus were particularly resistant to diazepam, all failing to show statistically significant decreases in conditioned fear-induced c-fos expression even at the highest dose. The extent to which diazepam decreased conditioned stress-induced c-fos expression was unrelated to previous estimates of benzodiazepine receptor density in the sampled structures.

Effects of D1 and D2 dopamine antagonists on behavior of polydipsic rats.

The behavioral and neurochemical effects of SCH3390 (SCH), a dopamine (DA) D1 antagonist, and haloperidol (HAL), a DA D2 receptor antagonist, on schedule-induced polydipsia (SIP) were examined. Once animals were made polydipsic, a vehicle or one of three doses of SCH or HAL were administered to seven groups of rats in a series of three five-session blocks in a drug condition, no-drug condition, drug condition design. Detailed behavioral measures and brain regional levels of monoamine neurotransmitters and their major acidic metabolites were analyzed. The volume of water consumed and the percent of time spent drinking was reduced dose dependently by both SCH and HAL. As drinking decreased, the time spent chewing increased for both drugs. The total amount of time animals engaged in all oral behaviors was not changed, suggesting that chewing was substituted for drinking. Neurochemical analysis revealed that HAL increased striatal DA significantly. The polydipsic paradigm may be an advantageous model for examining neuroleptics due to SIP's sensitivity to extrapyramidal side effects.

Analysis of the ongoing behavior of rats in non-matching-to-sample: improved acquisition and performance is related to facilitation of investigation.

In a non-matching-to-sample task, rats were trained according to the conventional procedure in which the displacement of the sample object resulted in food reinforcement and termination of the sample period. Compared to these animals, rats given a longer duration sample period, and rats not reinforced with food for displacing the object in the sample period, improved their rate of acquisition and their accuracy of performance. Detailed behavioral observations indicated that improved discrimination was related to increased investigation of the objects in the sample period, reduced side preferences, and an inclination to examine both objects in the test period. The results suggest that more accurate performance was related to the generalization of sampling habits from the sample period to the test period.

Food granules elicit heavy drinking in polydipsic rats independently of meal duration.

Excessive drinking, in rats made polydipsic on intermittent delivery of food pellets, is inversely related to the time the rat spends with its head in the feeder, early in the interfood interval. In a sensitization model, this explains why food textures that induce more oral activity, e.g., powder, do not elicit drinking. This hypothesis was examined by coding the behavior of polydipsic rats and varying the duration of the meal delivered in each interval, while holding texture constant. Polydipsic rats were presented with pellets, food granules, or food powder. The food granules were dispensed over periods lasting 1, 14, 21, and 28 s. All food deliveries were of the same mass. The food was delivered periodically at 60-s intervals in each condition. The 14 rats in the experiment served as their own controls by experiencing every condition. The food granule conditions induced the expected increases in feeding early in the interval. However, instead of progressively reducing drinking, the excessive drinking simply occurred later in the interval. By contrast, the powder condition resulted in the immediate elimination of polydipsia. The results suggest that food texture elicits excessive drinking independently of temporal factors and that elicitation of the sensitized drinking response must depend on other factors.

Behavioral analysis of diazepam-induced memory deficits: evidence for sedation-like effects.

Rats were trained on a nonmatching-to-sample task with delays of 2, 5, and 10 min. Subsequently, performance was assessed in three groups of rats following treatment with saline or diazepam (2.0 mg/kg) administered acutely or tested chronically in six administrations. Relative to treatment with saline, diazepam produced a deficit in discrimination performance, which was greater in the acutely treated rats than in those treated chronically. The deficit was not dependent on the length of the delays. Diazepam-treated animals differed from controls in erring on trials in which they failed to investigate both test objects, failed to investigate the test object for a long enough period of time, and displaced the test object on the preferred side of the apparatus. The hypothesis that these effects represented a sedation-like reduction in behavioral variability was also supported by evidence of a diazepam-induced decrease in gross bodily activity, increase in inactivity, and increase in latencies to respond to objects. No support was found for the involvement of diazepam-induced changes in habituation, extinction, or reward effects.

Diazepam effects on the exploratory behaviour of rats in an elevated runway: evidence for biphasic effects of benzodiazepines.

The purpose of this study was to test the validity of the fear-reduction model of benzodiazepine (BZ) action on the exploration of novelty. According to this hypothesis an animal given a tranquilizer should selectively increase the amount of investigative behaviour in the more novel portion of an elevated maze. To permit comparison of the same behaviours at both ends of the maze, an elevated runway was built with a wall running lengthwise along the midline of one end. In the first experiment, male Sprague-Dawley rats treated with diazepam (2.0 mg/kg, i.p., -30 min) compared to saline-treated animals, increased the time spent exploring the open end of the runway but not the wall end of the runway, thus supporting the fear-reduction model. However, saline-treated animals, made less fearful by repeated prior exposure to the runway, did not show a similar increase in open-end exploration. Instead, they habituated to the novelty of the runway, as grooming and sitting still replaced investigation. In Experiment 2, exploration was rewarded by adding to the open end of the runway a patch of litter soiled by a female rat. This produced a behavioural pattern in naive saline-treated rats very similar to that seen in naive diazepam-treated rats in the first experiment. In Experiment 3, diazepam potentiated the habituation of rats previously familiarized with the runway. The initial increase and subsequent decrease in exploration caused by diazepam were encompassed by the biphasic model of BZ action more adequately than either the fear-reduction or reward-enhancement models.

Reduced behavioral variability in extinction: effects of chronic treatment with the benzodiazepine, diazepam or with ethanol.

Extinction of a food reinforced habit results in an increase in the variability of the response learned in acquisition and in the appearance of previously suppressed competing responses. The purpose of the present study was to examine the effects of chronically administered diazepam (0.0, 1.5, 3.0, or 6.0 mg/kg, IP, -30 min) or 10% ethanol (0.0, 1.0, 1.5, or 2.0 g/kg, IP, -15 min) on such behavioral variability in the extinction of radial maze performance. Eight groups of food deprived rats (n = 6) were given one of the forementioned doses for 2 sessions of baseline, 18 sessions of acquisition, and 5 sessions of extinction. In acquisition, eight rewards of two food pellets were obtained on each of three trials in each session. The food well at the end of each arm was rebaited when emptied by the animal, consequently an entry into any arm was reinforced. In baseline and extinction no food was available in the maze. Each session consisted of three 10-min trials. In extinction, compared to treatment with vehicle, both diazepam and ethanol treatments decreased the rate of the instrumental response, arm entry, and increased the variability of the instrumental response and of competing responses. Only the effects of the drugs on the competing responses in extinction were greater than those observed in acquisition. It was concluded that the interference-reduction model of drug action best described the magnitude of the drug effects and the variability-reduction model best predicted the direction of the effects.

Rats treated chronically with the benzodiazepine, diazepam or with ethanol exhibit reduced variability of behavior.

The hypothesis that chronic treatment with diazepam or with ethanol reduces behavioral variability, was tested on rats in a radial maze. Eight groups (n = 6) of male Sprague-Dawley rats were given one of eight treatments of diazepam (0.0, 1.5, 3.0 or 6.0 mg/kg, IP, -30 min) or of 10% ethanol (0.0, 1.0, 1.5, or 2.0 g/kg, IP, -15 min) for 2 sessions of baseline and 18 sessions of acquisition. Each session consisted of 3 trials of 8 rewards each. Emptied food wells were immediately rebaited so that an entry into any arm produced a reward of 2 food pellets. Both diazepam and ethanol produced a dose-dependent reduction in the variability of arm choice, reduction in the variability of angle of turn between arms, and reduction in the variability of goal-directed behavior. Correlations between these measures suggested they were not independent. The implications of these reductions in behavioral variability for other effects of anxiolytic drugs are described.

Schedule-induced polydipsia: attenuating effects of decreased size of food granulations.

The effect of food texture on the development of schedule-induced polydipsia was examined in six groups of rats (n = 8), each receiving one of six grades of food granulation. A seventh group received pellets. By the end of 15 sessions of FT 60-sec food delivery, rats receiving pellets and the coarser granulations had developed polydipsia. The volume of water drunk at asymptote by the remaining groups declined with decreased coarseness of the food. Ethological analyses of the behavioral repertoire of the rats during the fifteenth session showed that the polydipsic groups sustained their drinking throughout the session, rather than turning from ingestive to exploratory behaviors near the end of the session, as was the case with animals receiving finer granulations. The enhanced drinking induced by the coarser food texture was reciprocally related to the amount of time the animal spent with its head in the feeder hole during the period of maximum drinking. The results support the conclusion that the schedule-induced polydipsia traditionally demonstrated with pellets as the reinforcer is critically dependent on the fact that pellets are coarse in texture.

Initial environment influences amphetamine-induced stereotypy: subsequently environment change has little effect.

Saline-treated and amphetamine-treated (7 mg/kg, ip, immediate) male rats from a Sprague-Dawley substrain were observed in two test environments designed to elicit different investigative responses in normal rats. Snout contact with the substrate was generated by placing the rat in a small enclosed cage. Absence of snout contact was induced by placement of the rat on a square elevated platform. Detailed ethological records were kept of locomotion, rearing, sitting, grooming, gnawing, and sleeping throughout the 90-min session. Amphetamine-treated rats incorporated environmentally contingent bodily postures into their forms of stereotyped behavior. The postures were characteristic of those evinced initially by the saline-treated rats in the same test environment. The control rats showed appropriate changes in their investigative behavior when the apparatus was changed at 10 and at 30 min postinjection. The amphetamine-treated rats, however, were completely unresponsive to such changes at 30 min and only partially so at 10 min postinjection. It was concluded that there is a temporal gradient of decreasing readiness to modify repetitive behavior after a single, large dose of amphetamine.

beta-Carboline FG 7142-reduced aggression in male rats: reversed by the benzodiazepine receptor antagonist, Ro15-1788.

The beta-carboline FG 7142 decreases conspecific aggression in male hooded rats. The purpose of this study was to examine the effects of pretreatment with Ro15-1788 or chlordiazepoxide (CDP) in this paradigm. The six groups (n = 8) were saline, FG 7142 (5 mg/kg, immediate, IP), CDP (5 mg/kg, -10 min, IP), CDP (5 mg/kg, -10 min) plus FG 7142 (5 mg/kg, immediate), Ro15-1788 (10 mg/kg, -10 min, IP), and Ro15-1788 (10 mg/kg, -10 min) plus FG 7142 (5 mg/kg, immediate). Following injection of the more aggressive member of a pair of isolation-housed rats, the pair was observed in a living cage over four 6-min trials interpolated over a 40 min session. In the first 20 min after the injection FG 7142 decreased aggression, decreased the pinning of the other animal, and increased avoiding behavior. These effects were the opposite of those seen in the Ro15-1788-injected rats and Ro15-1788 pretreatment reversed the effects of FG 7142. CDP alone caused prolonged aggressive behavior but as a pretreatment only partially reversed the effects of FG 7142.

The effect of the beta-carboline FG 7142 on the behaviour of male rats in a living cage: an ethological analysis of social and nonsocial behaviour.

The effects of FG 7142, a beta-carboline benzodiazepine receptor partial inverse agonist, on the social behavior of pair-housed rats were investigated. Four 6-min dyadic social encounters in a living cage were observed in a paradigm in which one member of a pair of rats was injected. The four injection groups (n = 8) were vehicle control, and FG 7142 at 2.5, 5.0 and 10.0 mg/kg, respectively. All injections were administered 2 min before the start of the first observation trial. Compared to the effects of vehicle alone, FG 7142 decreased aggressive behaviour but did not change the level of total social interaction. Thus there were compensating increases in approaching and avoiding behaviours following the administration of FG 7142. Locomotion declined marginally and immobility increased in FG 7142-injected rats. FG 7142 decreased the incidence of self-grooming. The evidence is consistent with a relatively selective reduction in intraspecies aggression in male rats after the injection of the beta-carboline inverse agonist.

Dose-related response of male rats to apomorphine: snout contact in the open-field.

Apomorphine (0.01 to 5 mg/kg, SC) was administered to male rats observed singly in the open-field. The behavior of each rat was coded using a microprocessor during 3 preinjection and 9 postinjection trials of 6 min duration over a 2 hr session. The behavior categories included grooming, yawning, turning, nodding and gnawing, as well as snout contact and nonsnout contact variants of locomoting, rearing and sitting. Dose-dependent increases in the time spent in snout contact with the field surface were noted throughout the complete dose range. Both the peak and duration of the snout contact epoch increased with the dose of apomorphine. The integrated time spent in all types of snout contact proved to be the best behavioral measure for discriminating between doses of apomorphine even though the topography of snout contact response changed as a function of the dose.

p-Chlorophenylalanine and p-chloroamphetamine pretreatment of apomorphine-challenged rats: effects on solitary and social behavior.

Following an initial rise in locomotor activity, apomorphine in large doses causes a concurrent rise in brain serotonin levels, locomotor akinesia, and stereotypic gnawing. However, reports to date have failed to observe any effect of pretreatment with serotonin depletors parachlorophenylalanine (pCPA) or parachloroamphetamine (pCA) on apomorphine-induced stereotypy. In the present study the effects of pCPA (250 or 400 mg/kg i.p., 3 days) and pCA (6.4 or 10.4 mg/kg i.p., 3 days) pretreatment on apomorphine-induced (5.0 mg/kg s.c., 5 min) behavior of male rats in the open-field were compared. For half of the trials in the 78 min session, the rats were alone and for half of the trials they were paired with an untreated male rat. pCA pretreatment increased the frequency of line-crossing and of jumping, whereas pCPA pretreatment increased the duration of bouts of locomotion and gnawing. These behavioral differences may be related to the interaction of pCA and pCPA with dopaminergic subsystems in the brain.

Subacute apomorphine injections in rats: effects on components of behavioral stereotypy.

This study was aimed at documenting the changes in the frequency and duration of bouts of behavior of Sprague-Dawley male rats in the open-field following each of four injections of apomorphine (Apo, 5 mg/kg, sc, immediate), or normal saline, delivered at 3-day intervals. Independent quantification of locomotion, sniffing, rearing, grooming, inactivity, gnawing, nodding, and jumping was obtained continuously throughout the 78-min sessions. Apo eliminated grooming and inactivity on all sessions. The large increases in locomotion and sniffing seen in the Apo rats compared to the saline rats on the first session were sustained throughout subsequent sessions. However, the Apo-induced potentiation of nodding of the head and gnawing, seen acutely, declined across sessions. These observations reconcile inconsistencies in the literature on subacute Apo effects. Finally, the individual differences in behavioral scores of Apo-treated rats were more stable than were those of saline-treated rats. This finding supports evidence in the literature that individual differences in neurochemistry are more likely to be predicted from the behavioral scores of Apo-challenged rats than from the scores of untreated rats.

Solitary and social behavior of male rats in the open-field.

The short-term effects of anxiolytic drugs have been assessed with tests of social affiliative behavior in rats. These tests must be completed in a brief time span, yet must include measures both of solitary activity and social behavior to dissociate affiliative from sedative and hypermotive drug effects. This study demonstrates that a paradigm of observation of alternating periods of solitary and social behavior of male rats yields data in accord with facts known about rats tested in separate, uninterrupted periods of solitary and social behavior. Agreement was obtained on the reliability of group and intersession behavior, on the levels of behavior, on the changes in behavior over trials and on the correlations between behaviors characteristic of rats tested separately in the two situations.

P-chloroamphetamine and a side-chain fluorinated analog: effects on brain amine levels and behavior.

Reserpinized (1 mg/kg, IP-24 hr) and saline-pretreated male rats were subdivided into groups receiving p-chloroamphetamine (pCA, 5.2 mg/kg, IP), 1-fluoromethyl-2-p-chlorophenylethylamine (FpCA, 5.6 mg/kg, IP), or saline, 90 minutes before the testing of behavior in the open-field and 150 minutes before sacrifice for assay of brain levels of amines. FpCA and pCA produced identical investigative and social patterns of behavior in saline pretreated animals in spite of the fact that pCA reduced serotonin levels whereas FpCA did not. Both pCA and FpCA enhanced dopamine and noradrenaline levels compared to saline controls. The behavioral syndrome common to FpCA and pCA animals was one of increased sitting still, and decreased locomotion and self-grooming while alone, and decreased locomotion, and social behavior but increased sniffing of the environment while in the company of an untreated male rat. Reserpine pretreatment exacerbated this syndrome of inactivity in pCA more than in FpCA rats even though the reserpinized groups did not differ from each other in the concentrations of the three amines.