Susan Schenk

Cocaine self-administration in rats influenced by environmental conditions: implications for the etiology of drug abuse

The present study investigated the possibility of environmental factors as an explanation for between-subject differences in cocaine self-administration. Weaning rats (21 days) were housed in isolated or aggregated conditions for 6 weeks and were tested for intravenous cocaine self-administration (0.1-1.0 mg/kg/infusion). Rats housed in groups failed to reliably self-administer this drug whereas isolated rats readily acquired an operant to receive infusions of cocaine. These data suggest that environmental factors play a major role in determining individual differences in the propensity to self-administer cocaine and that, as such, they should be considered more seriously by those interested in the basis and treatment of drug abuse.

Age-dependent effects of isolation housing on the self-administration of ethanol in laboratory rats

Studies of the influence of housing conditions on ethanol self-administration have been inconsistent, with findings that isolation housing increases, decreases or produces no effects on ethanol intake. One possible explanation for these discrepant findings is that the effects of housing are dependent on the age at which the manipulation is performed. In the present experiment rats were housed from weaning or from age 65 days in either an isolated or grouped condition. After 12 weeks, they were tested for the voluntary oral self-administration of ethanol. Although all rats consumed comparable quantities of ethanol when lower concentrations were available, the rats isolated from weaning consumed significantly greater amounts of more concentrated ethanol than their group-housed counterparts. In contrast, there was no difference in ethanol consumption between isolated and grouped rats when they were differentially housed at maturity. These data suggest that an important determinant of ethanol intake in rats is related to environmental factors and that the influence of these factors is age-dependent.

An examination of heroin conditioning in preferred and nonpreferred environments and in differentially housed mature and immature rats.

The study addressed two issues. First, we examined the effectiveness of heroin as a conditioning agent in a preferred environment using a place preference paradigm. Four daily injections of 80 micrograms/kg (SC) of heroin HCl were paired with environments that rats initially found to be either preferred or non-preferred. In subsequent tests, only those that had experienced the drug effects in the non-preferred environment increased the percentage of time spent in that environment. Rats conditioned in the test chamber that was initially preferred failed to increase the amount of time spent in that chamber post-conditioning. These results suggest that the conditioned place preference paradigm does not simply assess the rewarding consequence of heroin injections. We also examined the effects of grouped and isolation housing conditions on the heroin-produced conditioned place preference. Rats were housed under these conditions either immediately post weaning or at 120 days of age. There was a difference between the magnitude of the place preference produced by 20 micrograms/kg heroin in the isolated but not in the group housed rats. When isolated at weaning the rats were less sensitive to the drug than were rats isolated at maturity. These data are discussed with particular reference to the development of the endogenous opioid system.

Differential effects of isolation housing on the conditioned place preference produced by cocaine and amphetamine

Rats were obtained at 21 days of age and were housed either in isolation or in groups of 4 for 6 weeks. They were then tested for their sensitivity to cocaine HCl (0.31, 0.62, 1.25 or 2.5 mg/kg) or d-amphetamine SO4 (0.031, 0.062, 0.125, 0.25 or 0.5 mg/kg) using a modified place preference paradigm. The isolated rats were insensitive to cocaine in this paradigm whereas the group-housed animals showed peak effects at the lowest dose of this drug. In contrast, there was no difference in sensitivity to amphetamine as a function of housing conditions. These data strengthen the notion that the effects of the early environment on drug sensitivity in the adult are specific to certain classes of drugs. Further, these data lend support to the notion that the effects of cocaine and amphetamine in the place preference paradigm are mediated by different neural systems.

The substrates for lateral hypothalamic and medial pre-frontal cortex self-stimulation have different refractory periods and show poor spatial summation ☆

Refractory periods of the substrates for lateral hypothalamic (LH) and medial pre-frontal cortex (MPFC) self-stimulation were behaviorally estimated. The beginning of recovery from refractoriness was estimated as the time at which recovery was 20% complete. In all 7 rats, this estimate differed substantially across sites, averaging 0.66 msec and 1.59 msec for the LH and MPFC substrates, respectively. The recovery of excitability approached asymptote later in the MPFC substrate (3.5 msec) than in the LH substrate (1.5 msec). These findings are consistent with the view that different fibers subserve the reinforcing consequences of LH and MPFC stimulation. This notion is strengthened by the observation that the rewarding effects of stimulation summated poorly when stimulating pulses were concurrently delivered to these two sites.

Isolation versus grouped housing in rats: differential effects of low doses of heroin in the place preference paradigm.

Male Long Evans rats were reared from weaning (21-23 days) either in isolation or in groups of four for 40 days. Animals were then individually introduced to a testing apparatus consisting of two distinct chambers. A modified place preference paradigm was used consisting of 3 phases: (1) An habituation phase (4 days) during which rats were allowed free access to the entire test apparatus for 15 min. periods daily; (2) A conditioning phase (4 days) during which rats were confined to their non-preferred side for 15 minutes each day immediately following subcutaneous injection of 0, 20, 40 and 80 micrograms/kg of heroin HCl; (3) A test phase (1 day) during which rats were again allowed free access to the testing chamber following injection of vehicle. The difference in time spent on the conditioned side during habituation and test periods was determined. The group-reared rats showed similar effects for all doses of heroin whereas the same magnitude of drug effect was attained only at the highest dose used in the isolated rats. This differential sensitivity to heroin in the place preference paradigm is discussed in terms of the modification of behavioral effects of opiates by environmental influences.

Isolation rearing decreases opiate receptor binding in rat brain

Abstract Male hooded rats were reared from weaning either in isolation or in groups (3–4 per cage) for 45 days. Their brains were then analyzed for opiate receptor binding. Results indicated that the isolation reared rats had a lower density of opiate receptors than those rats reared in aggregation. These finding are discussed in terms of the relevance of opiate receptor binding to the behavioral efficacy of opiate drugs.

Housing Conditions Fail to Affect the Intravenous Self-Administration of Amphetamine

Rats were housed either in isolation or in groups of 4 for 6 weeks following weaning (21 days). After this housing period, some of the rats were tested for the acquisition of intravenous self-administration of amphetamine (0.004-0.25 mg/kg/infusion) and others were tested for the locomotor activating effects of amphetamine (0-1.0 mg/kg, IP). In the self-administration tests, both the isolated and grouped rats readily acquired the operant to obtain drug infusions and exhibited dose-dependent behavior. These results are in direct contrast to those we have obtained concerning the influence of the environmental manipulation on cocaine self-administration. In those tests, only isolated rats self-administered cocaine. The results of the locomotor tests indicated that whereas the isolated rats were consistently more active, the dose/response curves for the effects of amphetamine on activity were parallel for the rats reared under the different housing conditions. Thus the environment has specific effects on behavior which may be a reflection of specific neurochemical effects of the manipulation.

Isolation housing decreases the effectiveness of morphine in the conditioned taste aversion paradigm

Male Long Evans rats were obtained at 21 days of age and were housed in either an aggregated (four per double cage) or isolated (one per single cage) condition for 6 weeks. They were then placed on a fluid deprivation schedule that allowed them access to fluids for 20 min daily. This schedule was maintained for the remainder of the experiment. Following habituation, sensitivity to morphine-induced conditioned taste aversion (CTA) was compared in the differentially housed rats. On the 1st day and every 5 days thereafter the rats were presented with a 0.1% solution of sodium saccharin for the 20-min drinking period, followed immediately by an injection of morphine (0, 2.5, 5.0, 10.0, or 20.0 mg/kg). On intervening days they received water as the fluid. No drugs were given on these days. There was no difference in baseline saccharin consumption as a function of housing condition. In comparison with the isolated rats, the grouped animals were more sensitive to the CTA-inducing properties of low doses of morphine. These data strengthen the already existing evidence for the influence of the early housing environment on drug sensitivity and provide additional support for the conclusion that variability in response to a number of drugs of abuse can be reduced by environmental means. Possible mechanisms for the differences between isolation and aggregation housed rats are discussed.

The substrates for self-stimulation of the lateral hypothalamus and medial prefrontal cortex: A comparison of strength-duration characteristics

The directly activated substrates for self-stimulation of the lateral hypothalamus (LH) and medial prefrontal cortex (MPFC) were described by comparing their strength-duration characteristics. The current required to maintain a half-maximal rate of lever pressing was traded off against the pulse duration while all other stimulation parameters were kept constant. In this manner, cathodal strength-duration curves were obtained at four LH and eight MPFC sites; anodal curves were obtained at two of the LH and six of the MPFC sites. In general, the cathodal LH curves had lower rheobases than the cathodal MPFC curves and continued to descend after the MPFC curves had levelled off. At short pulse durations, the anodal curves lay above the cathodal curves, a finding more pronounced in the LH data. The two sets of curves converged at the longer pulse durations. The differences in the strength-duration curves are consistent with the notion that different directly stimulated neurons are responsible for the rewarding effects of LH and MPFC stimulation. Anatomical and physiological properties that could account for these differences are discussed.