Neuroleptics block high- but not low-dose heroin place preferences: Further evidence for a two-system model of motivation.

The researchers studied whether 2 separate motivational systems in the brain underlie the rewarding effects of morphine. The brain stem tegmental pedunculopontine nucleus (TPP) is involved in mediating the motivational effects of opiates in nondeprived (drug-naive) rats, whereas dopamine transmission is necessary in mediating the motivational effects of opiates in deprived rats (opiate withdrawal). The results show that heroin's motivational properties obey the same boundary between a nondeprived and a deprived motivational state. Bilateral ibotenic acid lesions of the TPP blocked the acquisition of a place preference for an environment paired with 0.05 mg/kg heroin (a dose that induces no withdrawal aversion) but had no effect on place preference for an environment paired with 0.5 mg/kg heroin (a dose that does induce withdrawal aversion). Dopamine antagonist pretreatment produced the opposite pattern of results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic exposure to morphine does not alter the neural tissues subserving its acute rewarding properties: Apparent tolerance is overshadowing.

Drug-naive, but not morphine-dependent, rats preferred places paired with morphine (2 mg/kg) over unfamiliar neutral places. Both drug-naive and morphine-dependent rats preferred places paired with higher doses of morphine (20 mg/kg) over unfamiliar places. Lesions of the tegmental pedunculopontine nucleus (TPP) blocked the conditioned place preferences produced by both 2 and 20 mg/kg morphine in drug-naive rats but not the preferences produced by 20 mg/kg morphine in dependent rats. When morphine-dependent animals received withdrawal-alleviating doses of morphine (20 mg/kg) 3.5 hrs before pairing one environment with 2 mg/kg morphine, they showed morphine-conditioned place preferences that were abolished by TPP lesions. The apparent behavioral tolerance to the TPP-mediated rewarding effects may have resulted from overshadowing by separate withdrawal-related motivational mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intracerebroventricular ethanol-induced conditioned place preferences are prevented by fluphenazine infusions into the nucleus accumbens of rats.

The rewarding properties of centrally administered ethanol (EtOH) were examined using a conditioned place preference (CPP) test. Male rats subjected to bilateral intracerebroventricular (icv) infusions of EtOH (0-240 nmol) produced a dose-dependent preference for the drug-paired environment that was potentiated by concurrent intravenous (iv) administration of heroin (0.025 mg/kg). The role of mesolimbic dopamine (DA) pathways in the development of EtOH reward was then examined by challenging EtOH-treated rats with bilateral intra-accumbens shell applications of a DA receptor antagonist. Fluphenazine (10 or 50 μg/side), infused immediately prior to daily place conditioning trials, was found to reliably attenuate the development of CPPs produced by icv EtOH administration. When fluphenazine was administered into the nucleus accumbens shell prior to the final test trial only (i.e., in already conditioned rats), intra-accumbens shell DA receptor blockade was found to prevent the expression of CPPs produced by icv EtOH. In summary, rats form reliable learned preferences for EtOH-paired locations (CPPs) that are potentiated by iv heroin and whose acquisition and expression rely on intact DA functionality within the nucleus accumbens. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clonidine antagonizes the aversive effects of opiate withdrawal and the rewarding effects of morphine only in opiate withdrawn rats.

The researchers asked whether clonidine, an α?-noradrenergic agonist, would block selectively the motivational effects of opiate withdrawal and whether clonidine's effects would respect the boundary between nondeprived and deprived motivational states. In a place conditioning paradigm, clonidine (0.05 mg/kg ip) blocked the rewarding effects of morphine in opiate-withdrawn rats (as well as the aversive properties of withdrawal itself), but did not affect morphine place preferences (2 and 20 mg/kg) in drug-naive rats. Furthermore, clonidine blocked the acquisition of morphine (15 mg/kg), but not LiCI (15 mg/kg), conditioned taste aversions in water-deprived rats. The results suggest that the motivational system activated in deprived animals includes dopaminergic and noradrenergic components that are in series with each other. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholinergic influences on estrogen-dependent sexual behavior in female rats.

Examined the ability of cholinergic agents to influence hormone-dependent sexual behavior in Sherman rats. In Exp I, sexual behavior, indicated by the incidence of lordosis, was significantly increased in estrogen-treated Ss following bilateral infusion of a cholinergic receptor agonist, carbachol (.5 μg/cannula) into the medial preoptic area of the brain. Infusion of an artificial cerebrospinal fluid vehicle failed to facilitate lordosis. The incidence of lordosis was normally highest 15 min after carbachol infusion began to wane by 45 min, and had returned to control levels by 90 min. Centrally administered carbachol activated lordosis at lower levels of estrogen priming than did systemically administered progesterone. In Exp II, Ss brought into sexual receptivity by administration of estrogen and progesterone received preoptic infusions of an acetylcholine synthesis inhibitor, hemicholinium-3 (HC-3). Significant reductions in the incidence of lordosis were observed following bilateral infusion of HC-3 (1.25 μg/cannula). This inhibition of lordosis was prevented when carbachol (.5 μg/cannula) was infused along with HC-3. Results confirm the importance of cholinergic influences on sexual behavior in female rats. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurobiology of motivation: Double dissociation of two motivational mechanisms mediating opiate reward in drug-naive versus drug-dependent animals.

Separate brain manipulations double dissociate 2 motivational mechanisms underlying the rewarding effects of opiates. Lesions of the brain-stem tegmental pedunculopontine nucleus block the rewarding properties of morphine in drug-naive, but not in drug-dependent, rats. Neuroleptics (which block the action of the neurotransmitter dopamine) abolished opiate motivational effects in drug-dependent, but not in drug-naive, rats in place conditioning paradigms. This 2nd dopaminergic opiate reward mechanism mediates morphine's alleviation of the withdrawal distress associated with abstinence in opiate-dependent animals. Furthermore, neuroleptic-induced blockade of food-related motivational effects in food-deprived, but not in food-sated (non-food-deprived), animals suggests that the neural substrates of motivational events do not dissociate along the line between different rewarding stimuli but along the line between deprivation and nondeprivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different receptor mechanisms mediate the effects of endotoxin and interleukin-1 on female sexual behavior

Activation of the immune system by lipopolysaccharide (LPS) produces physiological, neuroendocrine and behavioral effects, some of which are mediated by cytokine production. We have previously shown that the cytokine interleukin-1 (IL-1) inhibits sexual behavior in female, but not male rats, while producing a comparable suppression of locomotion in both sexes. The present study examined the effects of LPS on sexual behavior and locomotion of male and female rats, and the involvement of IL-1 receptors in mediating the effects of IL-1 and LPS on females' behavior. Peripheral (i.p.) administration of LPS (50 or 250 microg/kg) significantly decreased sexual behavior in females, up to 6 h after administration, while it had no effect on male sexual behavior. However, locomotor activity, measured in the open-field test, was similarly reduced by LPS in both males and females. Pretreatment with the IL-1 receptor antagonist (IL-1ra) either i.p. (10 mg/kg) or intracerebroventricularly (i.c.v.) (50 microg/rat) did not prevent the inhibition of female sexual behavior and locomotion induced by either i.p. (50 microg/kg) or i.c.v. (200 or 400 ng/rat) administration of LPS, respectively. However, identical doses of IL-1ra significantly reversed the effects of IL-1beta, administered either i.p. (5 microg/kg) or i.c.v. (50 ng/rat), respectively. These results demonstrate that both LPS and IL-1beta produce marked inhibition of sexual behavior in female, but not in male rats. However, IL-1 receptors are not required for the effects of LPS on sexual behavior in female rats.     

Effects of endocrine state on sociosexual behavior of female rats tested in a complex environment.

Examined the influence of both natural and artificially induced endocrine states on the sociosexual behavior of female Long-Evans rats during 15-min behavioral observations in a complex testing apparatus that allowed Ss to control their contacts with sexually active and passive males and ovariectomized (OVX) females. Ss were either intact and in various stages of the estrous cycle or OVX and treated with estradiol benzoate (5–20 μg), estradiol plus progesterone (0.5 mg/kg), or vehicle. Factor analysis of the behavioral measures indicated separate loadings on a lordotic behavior factor, a factor for Ss' preference for proximity to OVX females or passive males; and a factor for Ss' locomotion between portions of the testing apparatus. Behavioral variables loading on these factors were influenced by endocrine state, but the nature of the relation between behaviors and endocrine state varied between factors. The utility of the present testing situation in investigations of the neuroendocrine substrates underlying the motivational aspects of feminine reproductive behavior is discussed. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amphetamine lowers brain stimulation reward (BSR) threshold in alcohol-preferring (P) and non-preferring (NP) rats: Regulation by D? and D? receptors in the nucleus accumbens.

Differences in the mesolimbic dopamine (DA) pathway that regulates alcohol preference may also increase sensitivity to the reinforcing effects of other drugs of abuse. In the present study, the curve-shift (rate-frequency) paradigm was used to quantify the interaction of amphetamine with the rewarding effects of lateral hypothalamic brain stimulation reward (BSR) in alcohol-preferring (P) and -nonpreferring (NP) rats. The role of D? and D? DA receptors of the nucleus accumbens (NAcc) in mediating the reward-potentiating effects of amphetamine was also determined. Animals were tested with randomly administered amphetamine (0.25, 0.75, 1.25 mg/kg ip), DA-receptor antagonists (SCH 23390 [2.0 μg, 5.0 μg]; eticlopride [2.0 μg, 5.0 μg]), or a combination of the 2 (SCH 23390 [2.0 μg, 5.0 μg] + 0.75 mg/kg amphetamine; eticlopride [2.0 μg, 5.0 μg] + 0.75 mg/kg amphetamine). Amphetamine produced comparable dose-related leftward shifts in the rate-frequency function for both P and NP rats, with a greater than 60% reduction observed in BSR threshold. On intervening days, baseline threshold was unaltered between tests and similar between rat lines. Unilateral infusion in the NAcc of either the D? or D? receptor antagonist produced rightward shifts in the rate-frequency function of amphetamine, completely reversing-attenuating its reward-enhancing effects. The results demonstrate that amphetamine produces similar threshold-lowering effects in both P and NP rats and that the reward-potentiating effects of amphetamine do not correlate with alcohol preference under the conditions of the present study. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine release in the medial preoptic area of female rats in response to hormonal manipulation and sexual activity.

Dopamine (DA) is responsive to hormonal manipulations and has been implicated in the regulation of female rat sexual behavior. In the present studies, extracellular DA levels were assessed in the medial preoptic area (MPOA) of ovariectomized female rats in response to exogenous ovarian hormones and during sexual activity. In female rats primed with a low dose of estradiol benzoate (2 μg), but not with a higher dose (20 μg), a 500-μg progesterone injection increased extracellular DA and facilitated copulatory behavior. Extracellular DA levels in the MPOA were further augmented during sexual interactions with a male rat in a nonpacing copulatory chamber by either perineal or vaginal stimulation. However, in a pacing chamber, DA efflux did not increase, although the metabolites rose significantly during copulation. Together, these findings suggest that extracellular DA in the MPOA responds to the hormonal state of the female rat and may contribute to her expression of sexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual reinforcement is blocked by infusion of naloxone into the medial preoptic area.

Determined whether infusions of naloxone into specific brain sites can block sexual reinforcement as evaluated with the conditioned place preference procedure. Methylnaloxonium (5 μg/cannula) was infused bilaterally either into the medial preoptic area (MPOA) or into the nucleus accumbens (NAC) of sexually experienced male rats. The MPOA was chosen because it is important for sexual behavior, and several opioid peptides have been shown to modify sexual behavior when infused there. The NAC appears to be a critical structure for drug-induced reward. Methylnaloxonium blocked place preference produced by ejaculation after infusion into the MPOA without affecting sexual behavior. Infusion of the antagonist into the NAC did not reduce the reinforcing properties of ejaculation. Data suggest that the MPOA may be a site where sexual reward is produced. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social facilitation of operant behavior in satiated rats.

Tested 24 male, Long-Evans hooded rats in 2 motivational states (hungry and satiated) and 2 social conditions (single and paired) in adjacent and communicating Skinner boxes for the effect of a social stimulus on operant behavior. The social stimulus interfered in all conditions except 1: satiated Ss paired with hungry Ss pressed the bar significantly more often than in any other condition. It is concluded that the social facilitation effect is produced by progressive changes in the motivational state of the S as well as by a set of stimuli triggering the operant behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Concurrent inhibition of sexual behavior, but not brain [–3H]estradiol uptake, by progesterone in female rats.

In 7 experiments with ovariectomized female Sprague-Dawley rats, chronic injections of high doses of progesterone (5 mg) and low doses of estradiol benzoate (EB; 2 μg) resulted in less sexual behavior than did low doses of progesterone (.5 mg) and low doses of EB. In a typical procedure for inducing sexual behavior, EB and progesterone were given sequentially, separated by 42 hrs. High levels of progesterone (2.5 and 5 mg) administered concurrently with EB inhibited the induction of sexual receptivity. Increasing the dose of EB from 2 μg to 6 μg or 10 μg offset this inhibition. High doses inhibited the induction of sexual behavior, but the inhibition waned when progesterone was administered 48 hrs prior to EB. A single injection of progesterone (1 mg) that did not inhibit the induction of sexual behavior when administered concurrently with EB did inhibit lordosis when distributed into 5 injections (.2 mg) every 4 hrs. Results of 2 experiments in which progesterone did not inhibit the uptake or retention of [–3H]estradiol by brain cell nuclei suggest that the antiestrogenic action of progesterone in the CNS is not to interfere with the binding of estradiol. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modifications induced by neonatal steroids in reproductive organs and behavior of male rats.

112 3-day-old male Sprague-Dawley rats were injected neonatally with .01, .1, 1, 10, 100, or 1,000 μg of estradiol benzoate (EB), 10,000 μg of testosterone propionate (TP), or sesame oil; they were subsequently examined for testicular, penile, and accessory organ development. Sexual behavior was evaluated during therapy with fluoxymesterone (FM) and then with TP. EB in dosages greater than 1.0 μg delayed testicular descent, reduced the size and hormone responsiveness of reproductive organs, and decreased sexual behavior in a dose-dependent manner. The 10,000 μg dosage of neonatal TP delayed testicular descent and reduced sexual behavior to levels near those of the 10–200 μg EB groups, but it produced no significant penile or accessory organ changes. Neither reduced peripheral organ development nor inhibited neonatal testicular secretions fully explain reductions in male behavior following large dosages of neonatal TP. Neonatal androgen may reduce the responsiveness of CNS neurons governing male sexual behavior after being converted to estrogen or by directly altering steroid receptor systems. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of antimicrobial agents on the induction of tumour necrosis factor by alveolar macrophages in vitro in response to endotoxin

1. In the present study, we evaluated the role of repeated administration on conditioning place preference (CPP) induced by fencamfamine (FCF) in male rats. 2. Repeated FCF (3.5 mg/kg) or saline once or daily for ten consecutive days enhanced sniffing duration and decreased locomotion and rearing duration. 3. At the 3.5 mg/kg dose, FCF produced a significant place-preference effect. 4. Repeated exposures to FCF intensified its reinforcing properties. 5. These results suggest that repeated FCF administration sensitizes its rewarding effects, as with other addictive substances.     

Mesencephalic participation in the control of sexual behavior in the female rat.

In 2 experiments with 78 female albino rats, electric stimuli applied to both pudendal nerves evoked field potentials, unit responses, and multiunit responses in the ventrolateral midbrain, in and around the peripeduncular nucleus. Bilateral lesions placed in this region suppressed sexual behavioral responses (lordosis and courting behavior) of ovariectomized Ss primed with 5, 10, 100, and 1,000 μg of estradiol benzoate and 2 mg/kg progesterone. It is proposed that the region in question represents a relay station for the integration of sensory and endocrine information concerned in the control of receptive sexual behavior in the female rat. (54 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drug-induced hypothermia and conditioned place aversion.

Examined the relationship between ethanol's thermal and motivational effects in a place conditioning task. In 3 experiments, male albino rats were exposed to a differential conditioning procedure that paired a distinctive tactile stimulus with ethanol (1.2 or 1.8 g/kg) or lithium chloride (3 meq/kg); a different stimulus was paired with saline. Different groups were exposed to ambient temperatures (Ta) of 5°, 21°, or 32°C during each 60-min conditioning trial. Both ethanol and lithium chloride produced hypothermia and conditioned place aversion in rats conditioned at normal Ta. Exposure to high Ta reduced drug-induced hypothermia, increased activity, and decreased conditioned place aversion. Exposure to low Ta did not enhance drug-induced hypothermia or change conditioned place aversion. In general, these findings support the suggestion that the hedonic effects of ethanol and lithium chloride interact with their thermal effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Various aspects of feeding behavior can be partially dissociated in the rat by the incentive properties of food and the physiological state.

The authors investigated the role of food incentive properties and homeostatic state on the motivational, anticipatory, and consummatory aspects of feeding. Behavioral tests were carried out on food-sated and food-restricted rats that were presented with 2 kinds of food differing in their palatability level. Both food-sated and food-restricted rats consumed large quantities and were highly motivated when presented with very palatable food. In contrast, only food-restricted rats developed anticipatory responses, regardless of the kind of food presented. These data suggest that food incentive properties play a key role in the control of consummatory and motivational components of feeding but seem less involved in the regulation of anticipatory behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of osteocalcin and pyridinium crosslinks of bone collagen as markers of bone turnover in gingival crevicular fluid during different stages of orthodontic treatment

Treatment with serotonin reuptake inhibitors (SRIs) has been shown to cause reduced libido and anorgasmia in women. A large body of evidence suggests that serotonin may influence sexual behavior in estradiol + progesterone primed, gonadectomized female rats; however, the influence of selective SRIs on the estrous behavior of intact female rats has not been described previously. In the present study, the effect of 1 to 3 weeks of fluoxetine administration (10 mg/kg daily) on vaginal and behavioral estrus in intact female rats was studied; in addition, the effect of fluoxetine (same dose, 1-8 weeks) on copulatory behavior and on sexual motivation in hormone-primed gonadectomized rats was investigated. Subchronic administration of fluoxetine did not influence cyclicity as judged by the examination of vaginal smears but significantly reduced the percentage of rats displaying receptive behavior in the estrous phase. In addition, fluoxetine significantly reduced receptive behavior, including lordosis, in ovariectomized female rats primed with estradiol (6.25 micrograms/rat; -48 hr) plus progesterone (1.0 mg/rat, -4 hr); in contrast, sexual motivation--as reflected by the amount of time these rats elected to spend in the vicinity of a male rather than in the vicinity of a female or elsewhere--was little affected by the treatment.     

Toward an understanding of the influence of affective states on attentional tuning: Comment on Friedman and F?rster (2010).

Friedman and F?rster (2010) reviewed an extensive program of research that was consistent with the view that positive affective states broaden, whereas negative affective states narrow, the scope of attention. We applaud their creative investigations into these important psychological questions and appreciate their thorough review. However, recent evidence strongly suggests that the conclusions drawn by Friedman and F?rster need to be tempered, for the recent evidence suggests that motivational intensity rather than affective valence causes the modulations of attentional tuning. That is, affective states of low motivational intensity (e.g., sadness, postgoal positive affect) broaden attention, whereas affective states of high motivational intensity (e.g., disgust, pregoal positive affect) narrow attention. Our viewpoint is that attentional narrowing occurs during affective states of high motivational intensity to aid organisms in acquiring desirable objects and avoiding aversive ones. Attentional broadening occurs during affective states of low motivational intensity to open organisms to new opportunities. (PsycINFO Database Record (c) 2011 APA, all rights reserved)