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Previous studies have shown that Fischer 344 (F344) and Lewis (LEW) rats may differ with respect to their behavioural and neurochemical responses to several drugs of abuse, including amphetamines. Herein, we have examined whether such strain differences extend to a ring-substituted amphetamine, namely 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), a recreationally-used drug endowed with euphoric, but also long-term neurotoxic effects. Beside strain differences in baseline locomotor activity (F344>LEW), it was found that the subcutaneous administration of 10 mg/kg, but not 5 mg/kg, MDMA increased locomotor activity in F344 rats only. On the other hand, such a treatment increased to similar extents extracellular dopamine (DA) levels in the nucleus accumbens of F344 and LEW rats, thus suggesting that genetic differences in MDMA locomotor effects are not accounted for by accumbal DA release.

The spontaneously hypertensive rat (SHR) and Lewis rat strains differ in the elevated plus-maze of anxiety, the former and the latter strain displaying low and high anxiety, respectively. A recent study has shown that serotonin (5-hydroxytryptamine, 5-HT)2A receptor-mediated head shakes, but not [3H]ketanserin binding at these receptors, are less in Lewis rats, compared with SHRs. Herein, we have analysed the hypothesis of a difference in 5-HT2A receptor-effector coupling between these two strains. Confirming our previous results, the Bmax and KD values for the specific [3H]ketanserin binding at cortical 5-HT2A receptors were respectively identical in both strains. The accumulation of total inositol phosphates by the 5-HT2A,2B,2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 0.01-100 microM) was concentration- and strain (Lewis > SHR)-dependent. Preincubation with 0.01 and 0.1 microM of the 5-HT2A receptor antagonist SR 46349B, respectively, decreased and prevented DOI-elicited inositol phosphate production in both strains. The aforementioned genetic differences in 5-HT2A receptor-mediated head shakes may thus lie at some point distal from the 5-HT2A receptor.

Corticosteroids modulate the expression and/or functions of several serotonin (5-hydroxytryptamine; 5-HT) receptors. Conversely, analyses of the effects of corticosteroids upon 5-HT reuptake systems have been scarce and contradictory. Herein, the diurnal rhythm of midbrain [3H]citalopram binding to 5-HT transporters was analysed in sham and 11 day adrenalectomised rats. In addition, adrenalectomised rats were either complemented or not with corticosterone pellets (12.5-200 mg). Analyses of body weight increases and plasma adrenocorticotropic and corticosterone levels indicated that the protocol allowed the stimulation of mineralocorticoid receptors (MRs; 12.5 mg pellets) or the stimulation of both MRs and glucocorticoid receptors (GRs; 50-200 mg pellets). However, besides the observation of a slight, but significant diurnal (corticosteroid-independent) rhythm in 5-HT transporter binding (morning > evening), it was found that neither adrenalectomy nor corticosteroid receptor stimulation affected midbrain [3H]citalopram binding.