The purpose of the present study was to develop an animal model of nicotine self-administration that more closely approximates the conditions of human nicotine use than do existing models. In most nicotine self-administration models, rats acquire self-administration during brief daily sessions in which rapid injections of a relatively high dose of the drug, 0.03 mg/kg, serve as the reinforcer. The present study examined nicotine self-administration in rats that acquired the behavior while having virtually unlimited access to injections of a relatively low dose of the drug; the rats did not have any prior operant training or shaping. Under these conditions, rats readily acquire nicotine self-administration at doses at least as low as 0.00375 mg/kg per injection, and they self-administer throughout the active portion of their light cycle. The daily nicotine intake of rats, which ranged from 0.18 to 1.38 mg/kg per day, appears to be comparable to that of human smokers.

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Intravenous naloxone enhanced, and D-Ala2-Met-enkephalinamide (DALA) impaired, Pavlovian conditioned heart rate discrimination in rabbits (Oryctolagus cuniculus) during initial training trials, compared with saline; naloxone also delayed subsequent extinction of the discrimination. These effects of the opioid treatments on discrimination were abolished by parasagittal knife-cut lesions in the sublenticular substantia innominata that did not, themselves, impair discrimination. Both naloxone and DALA decreased the magnitude and altered the topography of bradycardiac conditioned responses, and the lesions also abolished these effects of the opioid treatments, but they did not alter the effect of naloxone to decrease bradycardiac orienting response magnitude. These findings suggest that fibers in the sublenticular area mediate specifically the effects of systemic opioids on associative functions during Pavlovian cardiac conditioning and extinction.

Systemically administered nicotine elicits ACTH release indirectly by acting on neurons in brainstem catecholaminergic regions known to send afferent projections to the paraventricular nucleus of the hypothalamus (PVN), the site of CRH neurons involved in initiating ACTH secretion. The present study in rats examined 1) the relationship between dose-dependent expression of cFos in the PVN and that in the nucleus of the solitary tract (NTS)-A2, NTS-C2 and locus coeruleus (LC), after iv nicotine (0.045-0.18 mg/kg, administered at 0.09 mg/kg per min); 2) the dependence of PVN cFos expression on the effects of nicotine in brainstem, using the nicotinic cholinergic antagonist, mecamylamine, administered into the fourth ventricle; and 3) the extent of catecholaminergic involvement in the effect of nicotine on the PVN, measured by immunocytochemical double-labeling for cFos and tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. The results showed that the magnitude of cFos expression was dependent on the dose of nicotine in all regions studied (P < 0.0006); however, at the two lowest doses, only the NTS and CRH-containing region of the PVN expressed cFos, whereas the LC and the rest of the PVN were activated only by higher doses. Nicotine also elicited a dose-dependent increase in cFos expression in the TH+ neurons of the NTS, with C2 more sensitive than A2. Interestingly, the majority of NTS neurons expressing cFos were noncatecholaminergic, implicating other transmitter systems. Fourth ventricular mecamylamine completely blocked nicotine-induced cFos expression throughout the NTS, as well as the PVN. The results provide further support for the idea that catecholaminergic afferents from the NTS, but not the LC, play a significant, albeit not an exclusive, role in the activation of the PVN in response to nicotine.

Demographic measures, psychosocial variables, and objective and subjective measures of physical impairment were assessed in elderly men twice at intervals of 12 to 18 months. Canonical discriminant function analysis of the relationship between these predictor variables on the first testing and whether participants (a) returned for retesting, (b) did not return because of apparent disinterest, or (c) did not return because of illness or death, revealed two significant canonical variates. The first, characterized by decreased mental and physical capacity, discriminated between the deceased/ill group and the other two groups. The second was characterized by decreased social interaction and life satisfaction, and increased life events, and distinguished between the disinterested group and the other two groups. However, both groups that failed to return for retesting showed evidence of impaired physical health and a general disengagement from social and personal activities, compared to the retested group.