Pilot Investigation of 2 Nondiet Approaches to Improve Weight and Health.

Context • Weight loss and maintenance are associated with many health benefits, but long-term maintenance of weight loss remains elusive for many people. Overweight individuals are at higher risk than normal-weight individuals for stress-induced overeating. The use of stress-management tools in a weight loss program might decrease the physiological stress that fuels overeating and improve posttreatment maintenance of weight loss Objective • The study intended to compare the differences in outcomes between 2 approaches to achieving weight loss and changes in health-stress reduction and intuitive eating (IE)-during a 14-wk period. Design • The research team designed a small, randomized, controlled pilot study. Setting • The study took place at the University of Kentucky (Lexington, KY, USA). Participants • Men and women, aged 25 to 65 y, with a body mass index ≥30 but ≤40 kg/m2, were recruited through various outlets on a large college campus, and 33 enrolled in the study. Intervention • Participants were randomly assigned either to an IE or to a stress-reduction program (EBT) for a 7 wk intervention and a 7-wk follow-up period. Outcome Measures • Weight, blood pressure, stress, depression, and eating behaviors were measured at baseline, postintervention at week 7, and postintervention at week 14. Results • Participants were 69.7% female and 93.9% Caucasian. An intent-to-treat analysis was conducted on the main outcome of weight. At 14 wk, the EBT group had lost 4.4 ± 6.7 lb (1.99 ± 3.04 kg), and the IE group had lost 1.03 ± 6.10 lb (0.48 ± 2.77 kg). A repeated measures analysis of variance did not find any significant difference between groups for weight change (P = .36). Completers in the EBT group significantly improved blood pressure, perceived stress, and food addiction symptoms from baseline to 7 wk (P < .05). Only the changes in weight were maintained at 14 wk. Conclusions • The study suggested that the stress reduction approach may be viable as an approach to weight loss and improvements in health-related outcomes in the short term. A longer investigation of the program is warranted.

Limbic pallidal adaptations following long-term cessation of dopaminergic transmission: lack of upregulation of dopamine receptor function.

Neurons in the ventral pallidum (VP) exhibit robust responding to activation of dopamine (DA) receptors of the D1 class. To determine if the VP adapts to chronic cessation of DA transmission, the present studies examined D1 receptor-mediated responses in the VP recorded extracellularly in chloral-hydrate anesthetized rats following destruction of DA neurons with 6-hydroxydopamine (6-OHDA) or long-term treatment with the D1 antagonist SCH23390. Indices of basal spiking (i.e., spontaneous firing rate and pattern) recorded 10-21 days after unilateral 6-OHDA treatment did not differ from controls. Moreover, DA depletion did not alter the proportion of VP neurons whose rate was enhanced with i.v. injections of the D1 agonist SKF38393, and the functional efficacy (Emax) and potency (ED50) were similar to controls. There also was no change in the direction of responses, the Emax or the ED50 measure of sensitivity (ECur50) to iontophoretic application of DA or SKF38393 in VP neurons. Forty-eight hours after 21 once-daily treatments with SCH23390, the number of [3H]SCH23390-labeled D1 receptors was increased in the striatum, but unchanged in the VP, globus pallidus, or septum. Accordingly, there was no functional upregulation of VP responses to i.v. SKF38393. Indeed, the proportion of SKF38393-sensitive neurons was decreased after chronic SCH23390. Distinguishing the VP from other forebrain regions, these findings indicate that basal spiking is not altered in the VP following chronic DA depletion, and that no upregulation of VP DA receptor function occurs following either dopaminergic lesions or chronic antagonism of D1 receptors.

Contribution of GIRK2-mediated postsynaptic signaling to opiate and alpha 2-adrenergic analgesia and analgesic sex differences.

The analgesia produced by inhibitory G protein-coupled receptor agonists involves coordinated postsynaptic inhibition via G protein-coupled inwardly rectifying potassium channels (GIRKs) and presynaptic inhibition of neurotransmitter release through regulation of voltage-gated Ca(2+) channels. Here, we used mice lacking the GIRK2 channel subunit to assess the relative contribution of these two effector systems to nociceptive processing in male and female mice. Compared with female WT mice, male WT mice exhibited higher pain thresholds and enhanced opioid (morphine) and alpha(2)-adrenergic (clonidine) receptor-induced antinociception in a spinal reflex test. The GIRK2-null mutation reduced the "pain" threshold in male but not in female mice, effectively eliminating the sex differences in pain threshold. In addition, deletion of GIRK2 channels in mutant mice largely eliminated clonidine antinociception and significantly decreased morphine antinociception. Furthermore, the more pronounced morphine and clonidine-induced antinociception in male mice disappeared in the GIRK2 mutants. Based on the almost complete loss of clonidine-induced antinociception in the mutant mice, we conclude that it is primarily mediated by postsynaptic alpha(2)-adrenergic receptors. In contrast, the significant residual morphine effect in the mutant mice points to the presynaptic mu opioid receptor as a major contributor to its analgesic action. Finally, our results suggest that the reduced pain responsiveness of male compared with female mice results in part from GIRK2-coupled postsynaptic receptors that are activated by endogenous antinociceptive systems.

Mu and kappa opioid agonists modulate ventral tegmental area input to the ventral pallidum.

The ventral pallidum (VP) is situated at the convergence of midbrain dopamine and accumbal opioid efferent projections. Using in vivo electrophysiological procedures in chloral hydrate-anaesthetized rats, we examined whether discrete application of mu- [D-Ala2,N-Me-Phe4,Gly-ol5 (DAMGO)] or kappa- (U50488) opioid receptor agonists could alter VP responses to electrical stimulation of ventral tegmental area. Rate suppressions occurred frequently following ventral tegmental area stimulation. Consistent with an involvement of dopamine in this effect, none of the 12 spontaneously active ventral pallidal neurons recorded in rats that had monoamines depleted by reserpine responded to electrical stimulation of ventral tegmental area. Moreover, in intact rats, the dopamine antagonist flupenthixol attenuated evoked suppression in 100% of the neurons tested; however, the GABAA antagonist bicuculline was able to slightly attenuate the response in 50% of the neurons tested. These observations concur with our previous studies in indicating that ventral tegmental area stimulation releases dopamine (and sometimes GABA) onto ventral pallidal neurons. Both DAMGO and U50488 decreased the inhibitory effects of ventral tegmental area stimulation. These effects on the endogenously released transmitter differed from those seen with exogenously applied dopamine, for DAMGO did not alter the efficacy or potency of microiontophoretically applied dopamine. Taken together, these observations suggest that the interaction between DAMGO and dopamine does not occur at a site that is immediately postsynaptic to the dopaminergic input within the VP, but rather that opioid modulation involves mechanisms governing presynaptically released dopamine. These modulatory processes would enable ventral pallidal opioids to gate the influence of ventral tegmental area dopamine transmission on limbic system outputs at the level of the VP.